Black Cumin seed fights cancer elegantly.

Black Cumin seed fights cancer elegantly.

Dr. Weeks’ Comment:  Many medications derive from plants and this is true for chemotherapy agents also: Taxol from the pacific yew,  Etoposide from the Mayapple plant, Vincristine and Vinblastine from periwinkle leaves so you will not be surprised that the black cumin seed, a major ingredient in SOUL has itself potent and diverse anti-cancer properties – just like a medicine.   In addition, black cumin seed is anti0-inflammatory and top oncologists now know that the key to stopping lethal spreading of cancer (metastasis)  is to use safe and effective anti-finallatory agents  – such as what is offered by SOUL.  Read on and be amazed by the power of plants in fighting cancer.

 

Asian Pac J Cancer Prev. 2014;15(2):983-7.

Cytotoxicity of Nigella sativa seed oil and extract against human lung cancer cell line.

Author information

The data revealed that the treatment of seed extract (NSE) and seed oil (NSO) of Nigella sativa significantly reduce viability of human lung cancer cells.

Abstract

Nigella sativa (N sativa), commonly known as black seed, has been used in traditional medicine to treat many diseases. The antioxidant, anti-inflammatory, and antibacterial activities of N sativa extracts are well known. Therefore, the present study was designed to investigate the anticancer activity of seed extract (NSE) and seed oil (NSO) of N sativa against a human lung cancer cell line. Cells were exposed to 0.01 to 1 mg/ml of NSE and NSO for 24 h, then percent cell viability was assessed by 3-(4, 5-dimethylthiazol-2yl)-2, 5-biphenyl tetrazolium bromide (MTT) and neutral red uptake (NRU) assays, and cellular morphology by phase contrast inverted microscopy. The results showed NSE and NSO significantly reduce the cell viability and alter the cellular morphology of A-549 cells in a concentration dependent manner. The percent cell viability was recorded as 75%, 50%, and 26% at 0.25, 0.5, and 1 mg/ml of NSE by MTT assay and 73%, 48%, and 23% at 0.25, 0.5, and 1 mg/ml of NSE by NRU assay. Exposure to NSO concentrations of 0.1 mg/ml and above for 24 h was also found to be cytotoxic. The decrease in cell viability at 0.1, 0.25, 0.5, and 1 mg/ml of NSO was recorded to be 89%, 52%, 41%, and 13% by MTT assay and 85%, 52%, 38%, and 11% by NRU assay, respectively. A-549 cells exposed to 0.25, 0.5 and 1 mg/ml of NSE and NSO lost their typical morphology and appeared smaller in size. The data revealed that the treatment of seed extract (NSE) and seed oil (NSO) of Nigella sativa significantly reduce viability of human lung cancer cells.

PMID:

 24568529

[PubMed – in process]

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2.
Pharmacogn Rev. 2013 Jul;7(14):117-120.

Thymoquinone in the clinical treatment of cancer: Fact or fiction?

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Therefore, it is appropriate that TQ should move from testing on the bench to clinical experiments.

Abstract

Thymoquinone (TQ) is the bioactive phytochemical constituent of the seeds oil of Nigella sativaIn vitro and in vivo research has thoroughly investigated the anticancer effects of TQ against several cancer cell lines and animal models. As a result, a considerable amount of information has been generated from research thus providing a better understanding of the anti-proliferating activity of this compound. Therefore, it is appropriate that TQ should move from testing on the bench to clinical experiments. The purpose of this review is to highlight the potential of TQ as an anticancer agent and the chances of this compound in the clinical treatment of cancer, with special attention on breast cancer treatment.

KEYWORDS:

Breast cancer, drug delivery, pharmacokinetics, thymoquinone

PMID:

 24347919

[PubMed – as supplied by publisher] PMCID:

PMC3841989

 

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3.
C R Biol. 2013 Nov-Dec;336(11-12):546-56. doi: 10.1016/j.crvi.2013.10.007. Epub 2013 Nov 19.

Thymoquinone causes multiple effects, including cell death, on dividing plant cells.

Author information

 It also inhibits proliferation and induces programmed cell death (apoptosis) in human skin cancer cells.

Abstract

Thymoquinone (TQ) is a major constituent of Nigella sativa oil with reported anti-oxidative activity and anti-inflammatory activity in animal cells. It also inhibits proliferation and induces programmed cell death (apoptosis) in human skin cancer cells. The present study sought to detect the influence of TQ on dividing cells of three plant systems and on expression of Bcl2-associated athanogene-like (BAG-like) genes that might be involved during the process of cell death. BAG genes are known for the regulation of diverse physiological processes in animals, including apoptosis, tumorigenesis, stress responses, and cell division. Synthetic TQ at 0.1mg/mL greatly reduced wheat seed germination rate, whereas 0.2mg/mL completely inhibited germination. An Evans blue assay revealed moderate cell death in the meristematic zone of Glycine max roots after 1h of TQ treatment (0.2mg/mL), with severe cell death occurring in this zone after 2h of treatment. Light microscopy of TQ-treated (0.2mg/mL) onion hairy root tips for 1h revealed anti-mitotic activity and also cell death-associated changes, including nuclear membrane disruption and nuclear fragmentation. Transmission electron microscopy of TQ-treated cells (0.2mg/mL) for 1h revealed shrinkage of the plasma membrane, leakage of cell lysate, degradation of cell walls, enlargement of vacuoles and condensation of nuclei. Expression of one BAG-like gene, previously associated with cell death, was induced 20 min after TQ treatment in Glycine max root tip cells. Thus, TQ has multiple effects, including cell death, on dividing plant cells and plants may serve as a useful system to further investigate the mechanisms underlying the response of eukaryotic cells to TQ.

© 2013. Published by Elsevier SAS.

KEYWORDS:

BAG domain, Bcl2-associated athanogene-like family, Cell death, IQ motif, Root tips, Stress response

PMID:

 24296078

[PubMed – in process]

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4.
PLoS One. 2013 Sep 9;8(9):e72882. doi: 10.1371/journal.pone.0072882. eCollection 2013.

Thymoquinone inhibits autophagy and induces cathepsin-mediated, caspase-independent cell death in glioblastoma cells.

Author information

 

our results describe a novel mechanism of action for TQ as an autophagy inhibitor selectively targeting glioblastoma cells.

 


Abstract

Glioblastoma is the most aggressive and common type of malignant brain tumor in humans, with a median survival of 15 months. There is a great need for more therapies for the treatment of glioblastoma. Naturally occurring phytochemicals have received much scientific attention because many exhibit potent tumor killing action. Thymoquinone (TQ) is the bioactive compound of the Nigella sativa seed oil. TQ has anti-oxidant, anti-inflammatory and anti-neoplastic actions with selective cytotoxicity for human cancer cells compared to normal cells. Here, we show that TQ selectively inhibits the clonogenicity of glioblastoma cells as compared to normal human astrocytes. Also, glioblastoma cell proliferation could be impaired by chloroquine, an autophagy inhibitor, suggesting that glioblastoma cells may be dependent on the autophagic pathway for survival. Exposure to TQ caused an increase in the recruitment and accumulation of the microtubule-associated protein light chain 3-II (LC3-II). TQ also caused an accumulation of the LC3-associated protein p62, confirming the inhibition of autophagy. Furthermore, the levels of Beclin-1 protein expression were unchanged, indicating that TQ interferes with a later stage of autophagy. Finally, treatment with TQ induces lysosome membrane permeabilization, as determined by a specific loss of red acridine orange staining. Lysosome membrane permeabilization resulted in a leakage of cathepsin B into the cytosol, which mediates caspase-independent cell death that can be prevented by pre-treatment with a cathepsin B inhibitor. TQ induced apoptosis, as determined by an increase in PI and Annexin V positive cells. However, apoptosis appears to be caspase-independent due to failure of the caspase inhibitor z-VAD-FMK to prevent cell death and absence of the typical apoptosis related signature DNA fragmentation. Inhibition of autophagy is an exciting and emerging strategy in cancer therapy. In this vein, our results describe a novel mechanism of action for TQ as an autophagy inhibitor selectively targeting glioblastoma cells.

PMID:

 24039814

[PubMed – in process] PMCID:

PMC3767730

 

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5.
Molecules. 2013 Sep 12;18(9):11219-40. doi: 10.3390/molecules180911219.

Thymoquinone induces mitochondria-mediated apoptosis in acute lymphoblastic leukaemia in vitro.

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In conclusion, the results from the current study indicated that TQ could be a promising agent for the treatment of leukemia.

Abstract

There has been a growing interest in naturally occurring compounds from traditional medicine with anti-cancerpotential. Nigella sativa (black seed) is one of the most widely studied plants. This annual herb grows in countries bordering the Mediterranean Sea and India. Thymoquinone (TQ) is an active ingredient isolated fromNigella sativa. The anti-cancer effect of TQ, via the induction of apoptosis resulting from mitochondrial dysfunction, was assessed in an acute lymphocyte leukemic cell line (CEMss) with an IC50 of 1.5 µg/mL. A significant increase in chromatin condensation in the cell nucleus was observed using fluorescence analysis. The apoptosis was then confirmed by Annexin V and an increased number of cellular DNA breaks in treated cells were observed as a DNA ladder. Treatment of CEMss cells with TQ encouraged apoptosis with cell death-transducing signals by a down-regulation of Bcl-2 and up-regulation of Bax. Moreover, the significant generation of cellular ROS, HSP70 and activation of caspases 3 and 8 were also observed in the treated cells. The mitochondrial apoptosis was clearly associated with the S phase cell cycle arrest. In conclusion, the results from the current study indicated that TQ could be a promising agent for the treatment of leukemia.

PMID:

 24036512

[PubMed – indexed for MEDLINE]

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6.
Pharmacognosy Res. 2013 Jul;5(3):200-6. doi: 10.4103/0974-8490.112428.

Cellular responses with thymoquinone treatment in human breast cancer cell line MCF-7.

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thymoquinone inhibition of breast cancer cell proliferation

Abstract

BACKGROUND:

Nigella sativa or black seed extract has been reported to show various medicinal benefits. Thymoquinone which is an active compound of its seed has been reported to contain anti-cancer properties.

OBJECTIVE:

The study addressed the anti-cancer efficiency of long-term in vitro treatment with thymoquinone towards human breast cancer cell lines MCF-7.

MATERIALS AND METHODS:

Cell proliferation was determined with CellTiter 96 Aqueous. Non-Radioactive Cell Proliferation Assay Kit. It was followed with trypan blue exclusion test to determine the percentage of viable cells. The study incorporated cell cycle assay to distinguish cell distribution at various cell cycle phases using Cycletest Plus DNA Reagent Kit. The apoptosis detection kit was used to determine the percentage of apoptotic and necrotic cells using flow cytometry.

RESULTS:

The 50% inhibitory concentration (IC50) value determined using the proliferation assay was 25 μM thymoquinone. Late apoptotic cell percentage increased rapidly when treatment duration was increased to 24 h with 25 and 100 μM thymoquinone. Further analysis using cell cycle assay showed thymoquinone inhibition of breast cancer cell proliferation at minimal dose 25 μM and led to S phase arrest significantly at 72 h treatment (P = 0.009). It was also noted elevation sub-G1 peak following treatment with 25 μM thymoquinone for 12 h. Increase in thymoquinone to 50 μM caused G2 phase arrest at each time-point studied.

CONCLUSION:

In general thymoquinone showed sustained inhibition of breast cancer cell proliferation with long-term treatment. Specificity of phase arrest was determined by thymoquinone dose.

KEYWORDS:

Apoptosis, MCF-7 cell line, cytotoxicity, long-term exposure, thymoquinone

PMID:

 23900121

[PubMed] PMCID:

PMC3719263

 

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7.
BMC Complement Altern Med. 2013 Jul 10;13:166. doi: 10.1186/1472-6882-13-166.

Induction of apoptosis in melanoma A375 cells by a chloroform fraction of Centratherum anthelminticum (L.) seeds involves NF-kappaB, p53 and Bcl-2-controlled mitochondrial signaling pathways.

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Together, our findings suggest CACF as a potential therapeutic agent against human melanoma malignancy.

Abstract

BACKGROUND:

Centratherum anthelminticum (L.) Kuntze (scientific synonyms: Vernonia anthelmintica;black cumin) is one of the ingredients of an Ayurvedic preparation, called “Kayakalp”, commonly applied to treat skin disorders in India and Southeast Asia. Despite its well known anti-inflammatory property on skin diseases, the anti-cancer effect of C. anthelminticum seeds on skin cancer is less documented. The present study aims to investigate the anti-cancer effect of Centratherum anthelminticum (L.) seeds chloroform fraction (CACF) on human melanoma cells and to elucidate the molecular mechanism involved.

METHODS:

A chloroform fraction was extracted from C. anthelminticum (CACF). Bioactive compounds of the CACF were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Human melanoma cell line A375 was treated with CACF in vitro. Effects of CACF on growth inhibition, morphology, stress and survival of the cell were examined with MTT, high content screening (HSC) array scan and flow cytometry analyses. Involvement of intrinsic or extrinsic pathways in the CACF-induced A375 cell death mechanism was examined using a caspase luminescence assay. The results were further verified with different caspase inhibitors. In addition, Western blot analysis was performed to elucidate the changes in apoptosis-associated molecules. Finally, the effect of CACF on the NF-κB nuclear translocation ability was assayed.

RESULTS:

The MTT assay showed that CACF dose-dependently inhibited cell growth of A375, while exerted less cytotoxic effect on normal primary epithelial melanocytes. We demonstrated that CACF induced cell growth inhibition through apoptosis, as evidenced by cell shrinkage, increased annexin V staining and formation of membrane blebs. CACF treatment also resulted in higher reactive oxygen species (ROS) production and lower Bcl-2 expression, leading to decrease mitochondrial membrane potential (MMP). Disruption of the MMP facilitated the release of mitochondrial cytochrome c, which activates caspase-9 and downstream caspase-3/7, resulting in DNA fragmentation and up-regulation of p53 in melanoma cells. Moreover, CACF prevented TNF-α-induced NF-κB nuclear translocation, which further committed A375 cells toward apoptosis.

CONCLUSIONS:

Together, our findings suggest CACF as a potential therapeutic agent against human melanoma malignancy.

PMID:

 23837445

[PubMed – indexed for MEDLINE] PMCID:

PMC3718627

 

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8.
Bioorg Med Chem Lett. 2013 May 15;23(10):3101-4. doi: 10.1016/j.bmcl.2013.03.003. Epub 2013 Mar 14.

Synthesis, characterization and anti-tumor activity of novel thymoquinone analogs against pancreatic cancer.

Abstract

Thymoquinone (TQ), isolated from the seeds of Nigella sativa, show moderate efficacy against pancreaticcancer. In the present work we report synthesis and characterization of novel TQ analogs appended with gallate and fluorogallate pharmacophores and evaluation of their effects against pancreatic cancer cell lines for cell viability and induction of apoptosis. The efficacy of the analogs alone or in combination with Gemcitabine was assessed in vitro. LC-MS spectra of ATQTHB and ATQTFB showed major peaks corresponding to expected M+1 fragment at 316.34 and 322.34 respectively. Molecular docking studies revealed good fit for these analogs in the COX-2 protein cavity with better binding energies compared to parent TQ compound. Present TQ analogs exhibit superior anti-proliferative activity, excellent chemo-sensitizing activity against pancreatic cancer in vitro and in combination with Gemcitabine.

Copyright © 2013 Elsevier Ltd. All rights reserved.

PMID:

 23562242

[PubMed – indexed for MEDLINE]

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9.
Nat Prod Commun. 2013 Feb;8(2):213-6.

Methanolic extract of Nigella sativa seed inhibits SiHa human cervical cancer cell proliferation through apoptosis.

Abstract

Nigella sativa (NS), also known as black cumin, has long been used in traditional medicine for treating variouscancer conditions. In this study, we sought to investigate the potential anti-cancer effects of NS extract using SiHa human cervical cancer cells. NS showed an 88.3% inhibition of proliferation of SiHa human cervicalcancer cells at a concentration of 125 microL/mL methanolic extract at 24 h, and an IC50 value 93.2 microL/mL. NS exposure increased the expression of caspase-3, -8 and -9 several-fold. The analysis of apoptosis by Dead End terminal transferase-mediated dUTP-digoxigenin end labeling (TUNEL) assay was used to further confirm that NS induced apoptosis. Thus, NS was concluded to induce apoptosis in SiHa cell through both p53 and caspases activation. NS could potentially be an alternative source of medicine for cervical cancer therapy.

PMID:

 23513732

[PubMed – indexed for MEDLINE]

10.
BMC Complement Altern Med. 2012 Mar 29;12:25. doi: 10.1186/1472-6882-12-25.

Modulation of apoptosis in human hepatocellular carcinoma (HepG2 cells) by a standardized herbal decoction of Nigella sativa seeds, Hemidesmus indicus roots and Smilax glabra rhizomes with anti- hepatocarcinogenic effects.

Abstract

BACKGROUND:

A standardized poly-herbal decoction of Nigella sativa seeds, Hemidesmus indicus roots and Smilax glabra rhizomes used traditionally in Sri Lanka for cancer therapy has been demonstrated previously, to have anti-hepatocarcinogenic potential. Cytotoxicity, antioxidant activity, anti-inflammatory activity, and up regulation of p53 and p21 activities are considered to be some of the possible mechanisms through which the above decoction may mediate its anti-hepatocarcinogenic action. The main aim of the present study was to determine whether apoptosis is also a major mechanism by which the decoction mediates its anti-hepatocarcinogenic action.

METHODS:

Evaluation of apoptosis in HepG2 cells was carried out by (a) microscopic observations of cell morphology, (b) DNA fragmentation analysis, (c) activities of caspase 3 and 9, as well as by (d) analysis of the expression of pro-apoptotic (Bax) and anti-apoptotic (Bcl-2) proteins associated with cell death.

RESULTS:

The results demonstrated that in HepG2 cells, the decoction can induce (a) DNA fragmentation and (b) characteristic morphological changes associated with apoptosis (nuclear condensation, membrane blebbing, nuclear fragmentation and apoptotic bodies). The decoction could also, in a time and dose dependent manner, up regulate the expression of the pro-apoptotic gene Bax and down regulate expression ofanti-apoptotic Bcl-2 gene (as evident from RT-PCR analysis, immunohistochemistry and western blotting). Further, the decoction significantly (p < .001) enhanced the activities of caspase-3 and caspase-9 in a time and dose dependent manner.

CONCLUSIONS:

Overall findings provide confirmatory evidence to demonstrate that the decoction may mediate its reported anti-hepatocarcinogenic effect, at least in part, through modulation of apoptosis.

PMID:

 22458551

[PubMed – indexed for MEDLINE] PMCID:

PMC3364896

 

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11.
Biochem Biophys Res Commun. 2012 Jan 13;417(2):864-8. doi: 10.1016/j.bbrc.2011.12.063. Epub 2011 Dec 20.

Thymoquinone inhibits growth and augments 5-fluorouracil-induced apoptosis in gastric cancer cells both in vitro and in vivo.

Abstract

Thymoquinone (TQ), a component derived from the bioactive constituent of black seed (Nigella sativa), has been shown to exert biological activity on various types of human cancers. However, there are few studies addressing its effects on gastric cancer. Here, we present the first report describing the chemosensitizing effect of thymoquinone and 5-fluorouracil (5-FU) on gastric cancer cells both in vitro and in vivo. Studies have shown that pretreatment with TQ significantly increased the apoptotic effects induced by 5-FU in gastriccancer cell lines in vitro. Moreover, we found that TQ enhanced the 5-FU-induced killing of gastric cancer cells by mediating the downregulation of the anti-apoptotic protein bcl-2, the upregulation of the pro-apoptotic protein bax, and the activation of both caspase-3 and caspase-9. In addition to the in vitro results, it has been shown that the combined treatment of TQ with 5-FU represents a significantly more effective antitumor agent than either agent alone in a xenograft tumor mouse model. These data suggest that the TQ/5-FU combined treatment induces apoptosis by enhancing the activation of both caspase-3 and caspase-9 in gastric cancercells. These results, which provide molecular evidence both in vitro and in vivo, support our conclusion that thymoquinone can activate caspase-3 and caspase-9 and thus result in the chemosensitisation of gastriccancer cells to 5-FU-induced cell death.

Copyright © 2011 Elsevier Inc. All rights reserved.

PMID:

 22206670

[PubMed – indexed for MEDLINE]

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12.
Am J Chin Med. 2011;39(6):1075-91.

Anticancer activity of Nigella sativa (black seed) – a review.

Abstract

Nigella sativa (N. sativa) seed has been an important nutritional flavoring agent and natural remedy for many ailments for centuries in ancient systems of medicine, e.g. Unani, Ayurveda, Chinese and Arabic Medicines. Many active components have been isolated from N. sativa, including thymoquinone, thymohydroquinone, dithymoquinone, thymol, carvacrol, nigellimine-N-oxide, nigellicine, nigellidine and alpha-hederin. In addition, quite a few pharmacological effects of N. sativa seed, its oil, various extracts and active components have been identified to include immune stimulation, anti-inflammation, hypoglycemic, antihypertensive, antiasthmatic, antimicrobial, antiparasitic, antioxidant and anticancer effects. Only a few authors have reviewed the medicinal properties of N. sativa and given some description of the anticancer effects. A literature search has revealed that a lot more studies have been recently carried out related to the anticancer activities of N. sativa and some of its active compounds, such as thymoquinone and alpha-hederin. Acute and chronic toxicity studies have recently confirmed the safety of N. sativa oil and its most abundant active component, thymoquinone, particularly when given orally. The present work is aimed at summarizing the extremely valuable work done by various investigators on the effects of N. sativa seed, its extracts and active principles against cancer. Those related to the underlying mechanism of action, derivatives of thymoquinone, nano thymoquinone and combinations of thymoquinone with the currently used cytotoxic drugs are of particular interest. We hope this review will encourage interested researchers to conduct further preclinical and clinical studies to evaluate the anticancer activities of N. sativa, its active constituents and their derivatives.

PMID:

 22083982

[PubMed – indexed for MEDLINE]

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13.
Invest New Drugs. 2012 Oct;30(5):1813-9. doi: 10.1007/s10637-011-9734-1. Epub 2011 Sep 1.

Anti-neoplastic agent thymoquinone induces degradation of α and β tubulin proteins in human cancer cells without affecting their level in normal human fibroblasts.

Abstract

The microtubule-targeting agents derived from natural products, such as vinca-alkaloids and taxanes are an important family of efficient anti-cancer drugs with therapeutic benefits in both haematological and solid tumors. These drugs interfere with the assembly of microtubules of α/β tubulin heterodimers without altering their expression level. The aim of the present study was to investigate the effect of thymoquinone (TQ), a natural product present in black cumin seed oil known to exhibit putative anti-cancer activities, on α/β tubulin expression in human astrocytoma cells (cell line U87, solid tumor model) and in Jurkat cells (T lymphoblastic leukaemia cells). TQ induced a concentration- and time-dependent degradation of α/β tubulin in both cancercell types. This degradation was associated with the up-regulation of the tumor suppressor p73 with subsequent induction of apoptosis. Interestingly, TQ had no effect on α/β tubulin protein expression in normal human fibroblast cells, which were used as a non-cancerous cell model. These data indicate that TQ exerts a selective effect towards α/β tubulin in cancer cells. In conclusion, the present findings indicate that TQ is a novel anti-microtubule drug which targets the level of α/β tubulin proteins in cancer cells. Furthermore, they highlight the interest of developing anti-cancer therapies that target directly tubulin rather than microtubules dynamics.

PMID:

 21881916

[PubMed – indexed for MEDLINE]

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14.
Afr J Tradit Complement Altern Med. 2011;8(5 Suppl):226-32. doi: 10.4314/ajtcam.v8i5S.10. Epub 2011 Jul 3.

Anticancer activities of Nigella sativa (black cumin).

Abstract

Nigella sativa has been used as traditional medicine for centuries. The crude oil and thymoquinone (TQ) extracted from its seeds and oil are effective against many diseases like cancer, cardiovascular complications, diabetes, asthma, kidney disease etc. It is effective against cancer in blood system, lung, kidney, liver, prostate, breast, cervix, skin with much safety. The molecular mechanisms behind its anticancer role is still not clearly understood, however, some studies showed that TQ has antioxidant role and improves body’s defense system, induces apoptosis and controls Akt pathway. Although the anti-cancer activity of N. sativa components was recognized thousands of years ago but proper scientific research with this important traditional medicine is a history of last 2∼3 decades. There are not so many research works done with this important traditional medicine and very few reports exist in the scientific database. In this article, we have summarized the actions of TQ and crude oil of N. sativa against different cancers with their molecular mechanisms.

KEYWORDS:

Anti-cancer mechanism, Antioxidant, Nigella sativa, Thymoquinone, Traditional medicine

PMID:

 22754079

[PubMed – indexed for MEDLINE] PMCID:

PMC3252704

 

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15.
Int Immunopharmacol. 2011 Feb;11(2):250-4. doi: 10.1016/j.intimp.2010.11.032. Epub 2010 Dec 9.

The protective effect of thymoquinone against sepsis syndrome morbidity and mortality in mice.

Abstract

Sepsis and septic shock are life threatening complications and most common cause of death in intensive care units. Thymoquinone, a constituent of Nigella sativa (black seed), holds exceptional promise as an anti-cancerand anti-inflammatory agent. No evidence has been published, however, whether this compound has a protective effect from sepsis-related morbidity, mortality and associated organ dysfunction. To examine this, two sets of mice (n=12 per group), with parallel control groups, were acutely treated with thymoquinone intraperitoneal injections of 1.0 and 2.0mg/kg body weight, and were subsequently challenged with endotoxin Gram-negative bacteria (LPS O111:B4). In another set of experiments, thymoquinone was administered at doses of 0.75 and 1.0mg/kg/day for three consecutive days prior to sepsis induction with live Escherichia coli. Survival of various groups was computed, and renal, hepatic and sepsis markers were quantified. Thymoquinone reduced mortality by 80-90% and improved both renal and hepatic biomarker profiles. The concentrations of IL-1α with 0.75 mg/kg thymoquinone dose was 310.8 ± 70.93 and 428.3 ± 71.32 pg/ml in the 1mg/kg group as opposed to controls (1187.0 ± 278.64 pg/ ml; P<0.05). Likewise, IL-10 levels decreased significantly with 0.75 mg/kg thymoquinone treatment compared to controls (2885.0 ± 553.98 vs. 5505.2 ± 333.96 pg/ml; P<0.01). Mice treated with thymoquinone also exhibited relatively lower levels of TNF-α and IL-2 (P values=0.1817 and 0.0851, respectively). This study gives strength to the potential clinical relevance of thymoquinone in sepsis-related morbidity and mortality reduction and suggests that human studies should be performed.

Copyright © 2010 Elsevier B.V. All rights reserved.

PMID:

 21145996

[PubMed – indexed for MEDLINE]

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16.
Mutat Res. 2011 Jan 10;706(1-2):28-35. doi: 10.1016/j.mrfmmm.2010.10.007. Epub 2010 Oct 30.

Thymoquinone up-regulates PTEN expression and induces apoptosis in doxorubicin-resistant human breast cancer cells.

Abstract

The use of innocuous naturally occurring compounds to overcome drug resistance and cancer recalcitrance is now in the forefront of cancer research. Thymoquinone (TQ) is a bioactive constituent of the volatile oil derived from seeds of Nigella sativa Linn. TQ has shown promising anti-carcinogenic and anti-tumor activities through different mechanisms. However, the effect of TQ on cell signaling and survival pathways in resistant cancercells has not been fully delineated. Here, we report that TQ greatly inhibits doxorubicin-resistant human breastcancer MCF-7/DOX cell proliferation. TQ treatment increased cellular levels of PTEN proteins, resulting in a substantial decrease of phosphorylated Akt, a known regulator of cell survival. The PTEN expression was accompanied with elevation of PTEN mRNA. TQ arrested MCF-7/DOX cells at G2/M phase and increased cellular levels of p53 and p21 proteins. Flow cytometric analysis and agarose gel electrophoresis revealed a significant increase in Sub-G1 cell population and appearance of DNA ladders following TQ treatment, indicating cellular apoptosis. TQ-induced apoptosis was associated with disrupted mitochondrial membrane potential and activation of caspases and PARP cleavage in MCF-7/DOX cells. Moreover, TQ treatment increased Bax/Bcl2 ratio via up-regulating Bax and down-regulating Bcl2 proteins. More importantly, PTEN silencing by target specific siRNA enabled the suppression of TQ-induced apoptosis resulting in increased cell survival. Our results reveal that up-regulation of the key upstream signaling factor, PTEN, in MCF-7/DOX cells inhibited Akt phosphorylation, which ultimately causes increase in their regulatory p53 levels affecting the induction of G2/M cell cycle arrest and apoptosis. Overall results provide mechanistic insights for understanding the molecular basis and utility of the anti-tumor activity of TQ.

Copyright © 2010 Elsevier B.V. All rights reserved.

PMID:

 21040738

[PubMed – indexed for MEDLINE] PMCID:

PMC3037029

 

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17.
Nutr Cancer. 2010;62(7):938-46. doi: 10.1080/01635581.2010.509832.

Review on molecular and therapeutic potential of thymoquinone in cancer.

Abstract

Thymoquinone (TQ) is the predominant bioactive constituent present in black seed oil (Nigella sativa) and has been tested for its efficacy against cancer. Here, we summarize the literature about TQ’s molecular mechanism of action and its ability to induce apoptosis and inhibit tumor growth in preclinical models. TQ hasanti-inflammatory effects, and it inhibits tumor cell proliferation through modulation of apoptosis signaling, inhibition of angiogenesis, and cell cycle arrest. Chemosensitization by TQ is mostly limited to in vitro studies, and it has potential in therapeutic strategy for cancer. The results favor efficacy and enhancement of therapeutic benefit against tumor cells resistant to therapy based on cellular targets that are molecular determinants for cancer cell survival and progression. There have been attempts to synthesize novel analogs of TQ directed toward superior effects in killing tumor cells with more enhanced chemosensitizing potential than parent TQ compound. Based on published reports, we believe that further in-depth studies are warranted including investigation of its bioavailability and Phase I toxicity profiling in human subjects. The results from such studies will be instrumental in advancing this field in support of initiating clinical trials for testing the effects of this ancient agent in cancer therapy.

PMID:

 20924969

[PubMed – indexed for MEDLINE]

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18.
Cell Signal. 2011 Jan;23(1):152-60. doi: 10.1016/j.cellsig.2010.08.015. Epub 2010 Aug 31.

Down-regulation of cyclic nucleotide phosphodiesterase PDE1A is the key event of p73 and UHRF1 deregulation in thymoquinone-induced acute lymphoblastic leukemia cell apoptosis.

Author information

 Thymoquinone (TQ), the active principle of Nigella sativa black seeds, has anti-proliferative properties on numerous cancer cell types…. Altogether, our results show that TQ induced an initial down-regulation of PDE1A with a subsequent down-regulation of UHRF1 via a p73-dependent mechanism. This study further proposes that PDE1A might be involved in the epigenetic code inheritance by regulating, via p73, the epigenetic integrator UHRF1. Our findings also suggest that a forced inhibition of PDE1A expression might be a new therapeutic strategy for the management of acute lymphoblastic leukemia.

Abstract

Thymoquinone (TQ), the active principle of Nigella sativa black seeds, has anti-proliferative properties on numerous cancer cell types. Others and we have previously reported that TQ acts as agent that triggers cell cycle arrest and apoptosis through either a p53- or p73-dependent pathway. However, the immediate targets recruited upon TQ-induced cytotoxicity have not yet been clearly identified. We therefore asked whether cyclic nucleotide phosphodiesterases (PDEs) could be involved in TQ-triggered pro-apoptotic reactivity; PDEs are regulators of intracellular levels of cyclic nucleotides and therefore can modulate cAMP and cGMP-dependent cell death pathways. Our results showed that TQ specifically repressed PDE1A expression in the acute lymphoblastic leukemia Jurkat cell line. This effect is concomitant with the previously described sequential deregulation of the expression of the tumor suppressor protein p73 and the epigenetic integrator UHRF1 (Ubiquitin-like, PHD Ring Finger 1). Interestingly, RNA-interference knock-down of PDE1A expression as well as decreased PDE1A expression induced growth inhibition of Jurkat cells, cell cycle arrest and apoptosis through an activation of p73 and a repression of UHRF1. Conversely, PDE1A re-expression counteracted the cellular pro-apoptotic effects of TQ in association with a p73 repression and UHRF1 re-expression. Altogether, our results show that TQ induced an initial down-regulation of PDE1A with a subsequent down-regulation of UHRF1 via a p73-dependent mechanism. This study further proposes that PDE1A might be involved in the epigenetic code inheritance by regulating, via p73, the epigenetic integrator UHRF1. Our findings also suggest that a forced inhibition of PDE1A expression might be a new therapeutic strategy for the management of acute lymphoblastic leukemia.

Copyright © 2010 Elsevier Inc. All rights reserved.

PMID:

 20807569

[PubMed – indexed for MEDLINE]

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19.
Saudi J Gastroenterol. 2010 Jul-Sep;16(3):207-14. doi: 10.4103/1319-3767.65201.

Comparative study of Nigella Sativa and triple therapy in eradication of Helicobacter Pylori in patients with non-ulcer dyspepsia.

Abstract

BACKGROUND/AIM:

A large number of diseases are ascribed to Helicobacter pylori (H. pylori), particularly chronic active gastritis, peptic ulcer disease and gastric cancer. Successful treatment of H. pylori infection with antimicrobial agents can lead to regression of H. pylori-associated disorders. Antibiotic resistance against H. pylori is increasing, and it is necessary to find new effective agents. Nigella sativa seed (NS), a commonly used herb, possesses in vitro anti-helicobacter activity. The present study was undertaken to evaluate the efficacy of NS in eradication of H. pylori infection in non-ulcer dyspeptic patients.

MATERIALS AND METHODS:

The study was conducted on 88 adult patients attending King Fahd Hospital of the University, Al-Khobar, Saudi Arabia, from 2007 to 2008, with dyspeptic symptoms and found positive for H. pylori infection by histopathology and urease test. Patients were randomly assigned to four groups, receiving i) triple therapy (TT) comprising of clarithromycin, amoxicillin, omeprazole [n= 23], ii) 1 g NS + 40 mg omeprazole (OM) [n= 21], iii) 2 g NS + OM [n= 21] or iv) 3 g NS + OM [n= 23]. Negative H. pylori stool antigen test four weeks after end of treatment was considered as eradication.

RESULTS:

H. pylori eradication was 82.6, 47.6, 66.7 and 47.8% with TT, 1 g NS, 2 g NS and 3 g NS, respectively. Eradication rates with 2 g NS and TT were statistically not different from each other, whereas H. pylori eradication with other doses was significantly less than that with TT (P < 0.05). Dyspepsia symptoms improved in all groups to a similar extent.

CONCLUSIONS:

N. sativa seeds possess clinically useful anti-H. pylori activity, comparable to triple therapy. Further clinical studies combining N. sativa with antibiotics are suggested.

PMID:

 20616418

[PubMed – indexed for MEDLINE] PMCID:

PMC3003218

 

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20.
J Ethnopharmacol. 2010 Sep 15;131(2):268-75. doi: 10.1016/j.jep.2010.06.030. Epub 2010 Jun 30.

Nigella sativa modulates splenocyte proliferation, Th1/Th2 cytokine profile, macrophage function and NK anti-tumor activity.

Author information

  We anticipate that Nigella sativa ingredients may be employed as effective therapeutic agents in the regulation of diverse immune reactions implicated in various conditions and diseases such as cancer.

Abstract

AIM OF THE STUDY:

Nigella sativa, also known as blackseed, has long been used in traditional medicine for treating various conditions related to the respiratory and gastrointestinal systems as well as different types of cancers. In this study, the potential immunomodulatory effects of Nigella sativa are investigated in light of splenocyte proliferation, macrophage function, and NK anti-tumor activity using BLAB/c and C57/BL6 primary cells.

MATERIALS AND METHODS:

Splenocyte proliferation was assessed by [(3)H]-thymidine incorporation. Griess assay was performed to evaluate NO production by macrophages. ELISA was performed to measure the level of cytokines secreted by splenocytes and macrophages. NK cytotoxic activity against YAC-1 tumor cells was examined by JAM assay.

RESULTS:

We demonstrate that the aqueous extract of Nigella sativa significantly enhances splenocyte proliferation in a dose-responsive manner. In addition, the aqueous extract of Nigella sativa favors the secretion of Th2, versus Th1, cytokines by splenocytes. The secretion of IL-6, TNFalpha, and NO; key pro-inflammatory mediators, by primary macrophages is significantly suppressed by the aqueous extract of Nigella sativa, indicating that Nigella sativa exerts anti-inflammatory effects in vitro. Finally, experimental evidence indicates that the aqueous extract of Nigella sativa significantly enhances NK cytotoxic activity against YAC-1 tumor cells, suggesting that the documented anti-tumor effects of Nigella sativa may be, at least in part, attributed to its ability to serve as a stimulant of NK anti-tumor activity.

CONCLUSIONS:

Our data present Nigella sativa as a traditionally used herb with potent immunomodulatory,anti-inflammatory, and anti-tumor effects. We anticipate that Nigella sativa ingredients may be employed as effective therapeutic agents in the regulation of diverse immune reactions implicated in various conditions and diseases such as cancer.

Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

PMID:

 20600757

[PubMed – indexed for MEDLINE]

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21.
Pharm Res. 2010 Jun;27(6):1146-58. doi: 10.1007/s11095-010-0145-3. Epub 2010 Apr 27.

Structure-activity studies on therapeutic potential of Thymoquinone analogs in pancreatic cancer.

Author information

 From our results, we conclude that three of our novel TQ analogs warrant further investigation against PC, especially in combination with conventional chemotherapeutic agents.

Abstract

PURPOSE:

Pancreatic cancer (PC) is one of the deadliest of all tumors. Previously, we were the first to show that Thymoquinone (TQ) derived from black seed (Nigella sativa) oil has anti-tumor activity against PC. However, the concentration of TQ required was considered to be high to show this efficacy. Therefore, novel analogs of TQ with lower IC(50) are highly desirable.

METHODS:

We have synthesized a series of 27 new analogs of TQ by modifications at the carbonyl sites or the benzenoid sites using single pot synthesis and tested their biological activity in PC cells.

RESULTS:

Among these compounds, TQ-2G, TQ-4A1 and TQ-5A1 (patent pending) were found to be more potent than TQ in terms of inhibition of cell growth, induction of apoptosis and modulation of transcription factor-NF-kappaB. We also found that our novel analogs were able to sensitize gemcitabine and oxaliplatin-induced apoptosis in MiaPaCa-2 (gemcitabine resistant) PC cells, which was associated with down-regulation of Bcl-2, Bcl-xL, survivin, XIAP, COX-2 and the associated Prostaglandin E2.

CONCLUSION:

From our results, we conclude that three of our novel TQ analogs warrant further investigation against PC, especially in combination with conventional chemotherapeutic agents.

PMID:

 20422266

[PubMed – indexed for MEDLINE] PMCID:

PMC3093961

 

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22.
Cancer Cell Int. 2009 Nov 27;9:29. doi: 10.1186/1475-2867-9-29.

Induction of apoptosis in HeLa cells by chloroform fraction of seed extracts ofNigella sativa.

Author information

 Western Blot and TUNEL results suggested that Nigella sativa seed extracts regulated the expression of pro- and anti- apoptotic genes, indicating its possible development as a potential therapeutic agent for cervical cancer upon further investigation.

Abstract

BACKGROUND:

Cancer remains one of the most dreaded diseases causing an astonishingly high death rate, second only to cardiac arrest. The fact that conventional and newly emerging treatment procedures like chemotherapy, catalytic therapy, photodynamic therapy and radiotherapy have not succeeded in reverting the outcome of the disease to any drastic extent, has made researchers investigate alternative treatment options. The extensive repertoire of traditional medicinal knowledge systems from various parts of the world are being re-investigated for their healing properties. This study progresses in the direction of identifying component(s) from Nigella sativa with anti cancer activity. In the present study we investigated the efficacy of Organic extracts of Nigella sativa seed powder for its clonogenic inhibition and induction of apoptosis in HeLa cancercell.

RESULTS:

Methanolic, n-Hexane and chloroform extracts of Nigella sativa seedz effectively killed HeLa cells. The IC50 values of methanolic, n-hexane, and chloroform extracts of Nigella sativa were 2.28 microg/ml, 2.20 microg/ml and 0.41 ng/ml, respectively. All three extracts induced apoptosis in HeLa cells. Apoptosis was confirmed by DNA fragmentation, western blot and terminal transferase-mediated dUTP-digoxigenin-end labeling (TUNEL) assay.

CONCLUSION:

Western Blot and TUNEL results suggested that Nigella sativa seed extracts regulated the expression of pro- and anti- apoptotic genes, indicating its possible development as a potential therapeutic agent for cervical cancer upon further investigation.

PMID:

 19943925

[PubMed] PMCID:

PMC2794855

 

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23.
HPB (Oxford). 2009 Aug;11(5):373-81. doi: 10.1111/j.1477-2574.2009.00059.x.

Anti-inflammatory effects of the Nigella sativa seed extract, thymoquinone, in pancreatic cancer cells.

Author information

Tq also inhibited the constitutive and TNF-alpha-mediated activation of NF-kappaB in PDA cells and reduced the transport of NF-kappaB from the cytosol to the nucleus.

Abstract

BACKGROUND:

Both hereditary and sporadic forms of chronic pancreatitis are associated with an increased risk of developing pancreatic ductal adenocarcinoma (PDA). Inflammation has been identified as a significant factor in the development of solid tumour malignancies. We have recently shown that thymoquinone (Tq), the major constituent of Nigella sativa oil extract, induced apoptosis and inhibited proliferation in PDA cells. Tq also increased p21 WAF1 expression, inhibited histone deacetylase (HDAC) activity, and induced histone hyperacetylation. HDAC inhibitors have been shown to ameliorate inflammation-associated cancer. In this study, we evaluated the anti-inflammatory potential of Tq in PDA cells in comparison with that of a specific HDAC inhibitor, trichostatin A (TSA).

METHODS:

PDA cells were treated with or without Tq (25-75 microM), with or without pre-treatment of tumour necrosis factor (TNF)-alpha (25 ng/ml). The effect of Tq on the expression of different proinflammatory cytokines and chemokines was analysed by real-time polymerase chain reaction (PCR). Luciferase-labelled promoter studies evaluated the effect of Tq on the transcription of monocyte chemoattractant protein-1 (MCP-1) and nuclear factor-kappaB (NF-kappaB). The effect of Tq on the constitutive and TNF-alpha-induced activation and nuclear translocation of NF-kappaB was examined by ELISA and immunohistochemistry.

RESULTS:

Tq dose- and time-dependently significantly reduced PDA cell synthesis of MCP-1, TNF-alpha, interleukin (IL)-1beta and Cox-2. At 24 h, Tq almost completely abolished the expression of these cytokines, whereas TSA had a less dramatic effect. Tq, but not TSA, significantly and dose-dependently reduced the intrinsic activity of the MCP-1 promoter. Tq also inhibited the constitutive and TNF-alpha-mediated activation of NF-kappaB in PDA cells and reduced the transport of NF-kappaB from the cytosol to the nucleus.

CONCLUSIONS:

Our data demonstrate previously undescribed anti-inflammatory activities of Tq in PDA cells, which are paralleled by inhibition of NF-kappaB. Tq as a novel inhibitor of proinflammatory pathways provides a promising strategy that combines anti-inflammatory and proapoptotic modes of action.

KEYWORDS:

Nigella sative, inflammation, pancreatic cancer, thymoquinone

PMID:

 19768141

[PubMed] PMCID:

PMC2742606

 

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24.
J Ayub Med Coll Abbottabad. 2008 Apr-Jun;20(2):25-7.

Oral and intraperitoneal LD50 of thymoquinone, an active principle of Nigella sativa, in mice and rats.

Author information

 The LD50 values presented here after intraperitoneal injection and oral gavages are 10-15 times and 100-150 times greater than doses of thymoquinone reported for its anti-inflammatory, anti-oxidant and anti-cancer effects.

Abstract

BACKGROUND:

Thymoquinone is the major active principle of Nigella sativa (N. sativa) and constitutes about 30% of its volatile oil or ether extract. N. sativa oil and seed are commonly used as a natural remedy for many ailments. Using modern scientific techniques, a number of pharmacological actions of N. sativa have been investigated including immunostimulant, anti-inflammatory, anticancer, antioxidant, antihistaminic, antiasthmatic, hypoglycemic, antimicrobial and antiparasitic. There are only few reports regarding the toxicity of thymoquinone.

METHODS:

The present study was carried out to determine LD50 of thymoquinone both in mice and rats, orally as well as intraperitoneall, by the method of Miller and Tainter. Autopsy and histopathology of liver, kidney, heart and lungs were also determined.

RESULTS:

The LD50 in mice after intraperitoneal injection was determined to be 104.7 mg/kg (89.7-119.7, 95% confidence interval) and after oral ingestion was 870.9 mg/kg (647.1-1094.8, 95% confidence interval). Whereas, LD50 in rats after intraperitoneal injection was determined to be 57.5 mg/kg (45.6-69.4, 95% confidence intervals) and after oral ingestion was 794.3 mg/kg (469.8-1118.8, 95% confidence intervals). The LD50 values presented here after intraperitoneal injection and oral gavages are 10-15 times and 100-150 times greater than doses of thymoquinone reported for its anti-inflammatory, anti-oxidant and anti-cancer effects.

CONCLUSION:

Thymoquinone is a relatively safe compound, particularly when given orally to experimental animals.

PMID:

 19385451

[PubMed – indexed for MEDLINE]

25.
Biomed Sci Instrum. 2008;44:434-40.

Effects of thymoquinone and selenium on the proliferation of mg 63 cells in tissue culture.

Author information

 These results indicate that the combined use of TQ and Se may be an effective treatment option against human osteosarcoma cells.

Abstract

Antioxidants are substances that function to protect cells from damage caused by unstable free radicals and reactive oxygen species (ROS). These agents are also quite successful in deterring certain disease processes specifically, cancer. Antioxidants help fight these excess free radicals or ROS by donating electrons to make a more stable chemical group. Thymoquinone (TQ) is a major active component of black seed (Nigella sativa) and has been used in the Middle East for centuries to treat disease processes. Selenium (Se), unlike TQ, is found in almost all human tissue and is classified as a trace element. Se has the ability to modify cells by acting as antioxidants, modifying redox status and thyroid hormone metabolism. The purpose of this study was to further examine the use of TQ, an extra-cellular anti-oxidant, and Se, an endogenous antioxidant on the proliferation of osteoblasts cells (MG 63) in tissue culture. MG 63 cells were treated with conventional low, medium and high doses of TQ and Se to obtain an optimal dose for combined treatment. Results and biochemical markers were evaluated at 24, 48 and 72 hours for all groups. The combined dose of TQ and Se produced decreased cell counts, increased cellular damage, decreased alkaline phosphatase levels, and decreased glutathione levels as compared to control (P>0.05). These results indicate that the combined use of TQ and Se may be an effective treatment option against human osteosarcoma cells.

PMID:

 19141954

[PubMed – in process]

26.
Braz J Med Biol Res. 2007 Jun;40(6):839-47.

Anti-tumor properties of blackseed (Nigella sativa L.) extracts.

Author information

 Protection against DEN-mediated carcinogenic changes in rat liver can be achieved by long term treatment with the DC comprised of N. sativa seeds

Abstract

The objective of the present study was to evaluate the in vitro and in vivo anti-cancer effect of Nigella sativa L.seed extracts. The essential oil (IC50 = 0.6%, v/v) and ethyl acetate (IC50 = 0.75%) extracts were more cytotoxic against the P815 cell line than the butanol extract (IC50 = 2%). Similar results were obtained with the Vero cell line. Although all extracts had a comparable cytotoxic effect against the ICO1 cell line, with IC50 values ranging from 0.2 to 0.26% (v/v), tests on the BSR cell line revealed a high cytotoxic effect of the ethyl acetate extract (IC50 = 0.2%) compared to the essential oil (IC50 = 1.2%). These data show that the cytotoxicity of each extract depends on the tumor cell type. In vivo, using the DBA2/P815 (H2d) mouse model, our results clearly showed that the injection of the essential oil into the tumor site significantly inhibited solid tumor development. Indeed, on the 30th day of treatment, the tumor volume of the control animals was 2.5 +/- 0.6 cm(3), whereas the tumor volumes of the essential oil-treated animals were 0.22 +/- 0.1 and 0.16 +/- 0.1 cm(3) when the animals were injected with 30 microL (28.5 mg)/mouse and 50 microL (47.5 mg)/mouse per 48 h (six times), respectively. Protection against DEN-mediated carcinogenic changes in rat liver can be achieved by long term treatment with the DC comprised of N. sativa seeds

PMID:

 17581684

[PubMed – indexed for MEDLINE]

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27.
J Carcinog. 2006 May 9;5:11.

A long-term investigation of the anti-hepatocarcinogenic potential of an indigenous medicine comprised of Nigella sativa, Hemidesmus indicus and Smilax glabra.

Author information

 Protection against DEN-mediated carcinogenic changes in rat liver can be achieved by long term treatment with the DC comprised of N. sativa seeds

Abstract

BACKGROUND:

A decoction comprised of Nigella sativa seeds, Hemidesmus indicus root bark and Smilax glabra rhizome is being recommended for cancer patients by a family of traditional medical practitioners of Sri Lanka. Previous investigations have demonstrated that a short term (10 weeks) treatment with the decoction can significantly inhibit diethylnitrosamine (DEN) mediated expression of Glutathione S-transferase P form (GST-P) in rat liver. The objective of the present investigation was to determine whether long term (16 months) treatment with the decoction would be successful in inhibiting in rat livers, not only DEN- mediated expression of GST-P, but also the carcinogen mediated development of overt tumours (OT) or histopathological changes leading to tumour development (HT).

METHODS:

Thirty-six male Wistar rats were divided into 3 groups of 12 each. Groups 1 and 2 were injected intraperitoneally (i.p) with DEN (200 mg/kg) while group 3 was injected normal saline (NS). Twenty-four hours later, decoction (DC; 6 g/kg body weight/day) was orally administered to group 1 rats, while groups 2 and 3 (DEN-control and normal control) were given distilled water (DW). Treatment with DC or DW continued for 16 months. At the end of the 9th month and 16th months (study 1 and study 2 respectively), six rats from each group were sacrificed, and livers observed for OT or HT, both visually and by subjecting liver sections to staining with Haemotoxylin and Eosin (H & E), Sweet’s Silver stain (for reticulin fibers), Periodic Acid Schiff (PAS) staining (for glycogen), and immunohistochemical staining (for GST-P).

RESULTS:

At the end of 9 months (study 1) a hepatocellular adenoma (HA) developed in one of the rats in the DEN + DW treated group (group 2). At the end of 16 months (study 2), livers of all rats of group 2 developed OT and HT. Large areas of GST-P positive foci were also observed. No OT, HT or GST-P positive foci were detected in any of the other groups.

CONCLUSION:

Protection against DEN-mediated carcinogenic changes in rat liver can be achieved by long term treatment with the DC comprised of N. sativa seeds, S. glabra rhizome and H. indicus root bark.

PMID:

 16684351

[PubMed] PMCID:

PMC1475831

 

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28.
Int J Oncol. 2004 Oct;25(4):857-66.

Thymoquinone extracted from black seed triggers apoptotic cell death in human colorectal cancer cells via a p53-dependent mechanism.

Author information

“These results indicate that TQ is anti-neoplastic and pro-apoptotic against colon cancer cell line HCT116. The apoptotic effects of TQ are modulated by Bcl-2 protein and are linked to and dependent on p53. Our data support the potential for using the agent TQ for the treatment of colon cancer.” 

Abstract

For centuries, the black seed (Nigella sativa) herb and oil have been used in Asia, Middle East and Africa to promote health and fight disease. Thymoquinone (TQ), the most abundant constituent present in black seed, is a promising dietary chemopreventive agent. We investigated the effects of thymoquinone (TQ) against HCT-116 human colon cancer cells and attempted to identify its potential molecular mechanisms of action. We report that TQ inhibits the growth of colon cancer cells which was correlated with G1 phase arrest of the cell cycle. Furthermore, TUNEL staining and flow cytometry analysis indicate that TQ triggers apoptosis in a dose- and time-dependent manner. Apoptosis induction by TQ was associated with a 2.5-4.5-fold increase in mRNA expression of p53 and the downstream p53 target gene, p21WAF1. Simultaneously, we found a marked increase in p53 and p21WAF1 protein levels but a significant inhibition of anti-apoptotic Bcl-2 protein. Co-incubation with pifithrin-alpha (PFT-alpha), a specific inhibitor of p53, restored Bcl-2, p53 and p21WAF1 levels to the untreated control and suppressed TQ-induced cell cycle arrest and apoptosis. p53-null HCT-116 cells were less sensitive to TQ-induced growth arrest and apoptosis. These results indicate that TQ is antineoplastic and pro-apoptotic against colon cancer cell line HCT116. The apoptotic effects of TQ are modulated by Bcl-2 protein and are linked to and dependent on p53. Our data support the potential for using the agent TQ for the treatment of colon cancer.

PMID:

 15375533

[PubMed – indexed for MEDLINE]

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29.
J Carcinog. 2003 Oct 18;2(1):6.

Protection against diethylnitrosoamine-induced hepatocarcinogenesis by an indigenous medicine comprised of Nigella sativa, Hemidesmus indicus and Smilax glabra: a preliminary study.

Author information

 Overall results indicate that the decoction comprised of N. sativa, S. glabra and H. indicus has the potential to protect rat liver against DEN induced hepatocarcinogenesis

Abstract

BACKGROUND:

A decoction comprised of Nigella sativa seeds, Hemidesmus indicus root and Smilax glabra rhizome is used to treat cancer patients in Sri Lanka. However, the anti-carcinogenic properties of this decoction have not been experimentally confirmed. The purpose of this study was to determine whether the above decoction could protect against chemically induce hepatocarcinogenesis.

METHODS:

The effects of this decoction on diethylnitrosamine (DEN) induced hepatocarcinogenesis were examined in male Wistar rats using the medium term bioassay system of Ito, based on a 2-step model of hepatocarcinogenesis. Rats were randomly divided into 6 groups of 10 each. Groups 1 to 4 were injected with DEN (200 mg/kg) to initiate carcinogenesis. Twenty-four hours later groups 1 and 2 were administered the decoction at 4 g/kg body weight/day (dose 1) and 6 g/kg body weight/day (dose 2), respectively. Group 3 and group 4 were given distilled water instead of the decoction and a suspension of garlic powder (20 g/kg body weight/day) in distilled water (positive control), respectively. Group 5 and 6 were injected with normal saline and twenty-four hours later group 5 was given distilled water (normal control) while group 6 was given decoction dose 2 (decoction control). Oral feeding continued for two weeks after which all rats were subjected to 2/3 partial hepatectomy to promote carcinogenesis. Oral feeding continued for eight more weeks. At the end of the 10th week, rats were sacrificed and samples of livers taken for immunohistochemical studies.Carcinogenic potential was scored by comparing the number, area and staining intensity of glutathione S-transferase placental form (GST-P) positive foci and the number of cells/cm2 of the positive foci in the livers of the six groups of rats.

RESULTS:

The number and area of DEN-mediated GST-P positive foci, number of cells/cm2 of foci and staining intensity of the foci were significantly (P > 0.001) reduced by the decoction and garlic in the order dose 2 = garlic >dose 1.

CONCLUSION:

Overall results indicate that the decoction comprised of N. sativa, S. glabra and H. indicus has the potential to protect rat liver against DEN induced hepatocarcinogenesis

PMID:

 14613573

[PubMed – as supplied by publisher] PMCID:

PMC272933

 

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30.
Eur J Cancer Prev. 1999 Oct;8(5):435-40.

Inhibition of benzo(a)pyrene-induced forestomach carcinogenesis in mice by thymoquinone.

Author information

 “The present data may indicate the potential of TQ, the main constituent of the volatile oil of Nigella sativa seed, as a powerful chemopreventive agent against BP-induced forestomach tumours in mice”

Abstract

The modulating effect of thymoquinone (TQ) on benzo(a)pyrene (BP)-induced forestomach tumours was investigated in female Swiss albino mice, receiving oral administration of BP at a dose of 1 mg twice weekly for 4 weeks. Administration of 0.01% of TQ in drinking water 1 week before, during and after BP treatment until the end of the experiment resulted in significant suppression of BP-induced tumourigenesis when compared with the group receiving BP alone. TQ inhibited both BP-induced forestomach tumour incidence and multiplicity by 70% and 67%, respectively. Lipid peroxide accumulation and decreased glutathione (GSH) content and glutathione-S-transferase (GST) and DT diaphorase activities were observed in the liver of BP-treated tumour-bearing mice. TQ alone showed a significant induction in the enzyme activities of hepatic GST and DT diaphorase. Mice treated with TQ along with BP showed almost normal hepatic lipid peroxides and GSH levels, and normal enzyme activities compared to the control group. The present data may indicate the potential of TQ, the main constituent of the volatile oil of Nigella sativa seed, as a powerful chemopreventive agent against BP-induced forestomach tumours in mice. The possible modes of action of TQ may be through its antioxidant and anti-inflammatory activities, coupled with enhancement of detoxification processes.

PMID:

 10548399

[PubMed – indexed for MEDLINE]

31.
Anticancer Res. 1998 May-Jun;18(3A):1527-32.

The in vitro anti-tumor activity of some crude and purified components of blackseed, Nigella sativa L.

Abstract

A crude gum, a fixed oil and two purified components of Nigella sativa seed, thymoquinone (TQ) and dithymoquinone (DIM), were assayed in vitro for their cytotoxicity for several parental and multi-drug resistant (MDR) human tumor cell lines. Although as much as 1% w/v of the gum or oil was devoid of cytotoxicity, both TQ and DIM were cytotoxic for all of the tested cell lines (IC50’s 78 to 393 microM). Both the parental cell lines and their corresponding MDR variants, over 10-fold more resistant to the standard antineoplastic agents doxorubicin (DOX) and etoposide (ETP), as compared to their respective parental controls, were equally sensitive to TQ and DIM. The inclusion of the competitive MDR modulator quinine in the assay reversed MDR Dx-5 cell resistance to DOX and ETP by 6- to 16-fold, but had no effect on the cytotoxicity of TQ or DIM. Quinine also increased MDR Dx-5 cell accumulation of the P-glycoprotein substrate 3H-taxol in a dose-dependent manner. However, neither TQ nor DIM significantly altered cellular accumulation of 3H-taxol. The inclusion of 0.5% v/v of the radical scavenger DMSO in the assay reduced the cytotoxicity of DOX by as much as 39%, but did not affect that of TQ or DIM. These studies suggest that TQ and DIM, which are cytotoxic for several types of human tumor cells, may not be MDR substrates, and that radical generation may not be critical to their cytotoxic activity.

PMID:

 9673365

[PubMed – indexed for MEDLINE]

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Dr. Weeks’ Comment:  Many medications derive from plants and this is true for chemotherapy agents also: Taxol from the pacific yew,  Etoposide from the Mayapple plant, Vincristine and Vinblastine from periwinkle leaves so you will not be surprised that the black cumin seed, a major ingredient in SOUL has itself potent and diverse anti-cancer properties…
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