More on Black Cumin Seed and Cancer

Dr. Weeks’ Comment:   A wise doctor is quick to know what he or she doesn’t know.  I strive for that wisdom and now confess to you, dear reader that for 99% of my professional career, I was entirely ignorant of the magnificent benefits of black cumin seed – known in many cultures as “the blessed seed” and “love in a mist”  and even lauded by the Prophet Mohammad in his Hadith as the one element on earth that “cures everything except death”.    Let’s look at the science…

 

1.  http://www.mskcc.org/cancer-care/herb/nigella-sativa

2.   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.

Gali-Muhtasib H, Diab-Assaf M, Boltze C, Al-Hmaira J, Hartig R, Roessner A, Schneider-Stock R.
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.

 

 

3. Photochem Photobiol. 2006 Nov-Dec;82(6):1691-6.

In vivo radioprotective effects of Nigella sativa L oil and reduced glutathione against irradiation-induced oxidative injury and number of peripheral blood lymphocytes in rats.

Cemek M, Enginar H, Karaca T, Unak P.

Source

Department of Chemistry, Biochemistry Division, Faculty of Science and Arts, Afyon Kocatepe University, Afyon, Turkey. mcemek@yahoo.com

Abstract

Radiotherapy is one of the most common therapies for treating human cancers. Several studies have indicated that irradiation induces reactive oxygen species (ROS), which play an important role in radiation damage of the cell. It has been shown that Nigella sativa L. (NS) and reduced glutathione (GSH) have both an antiperoxidative effect on different tissues and a scavenger effect on ROS. The purpose of this study was to determine the antioxidant and radio-protective roles of NS and GSH against irradiation-induced oxidative injury in an experimental model. The NS group was administrated NS (1 mL/kg body weight), the GSH group was injected GSH (150 mg/kg body weight) and the control group was given physiologic saline solution (1 mL/kg body weight) for 30 consecutive days before exposure to a single dose of 6 Gy of radiation. Animals were sacrificed after irradiation. Malondialdehyde, nitrate, nitrite (oxidative stress markers) and ascorbic acid, retinol, beta-carotene, GSH and ceruloplasmin (nonenzymatic antioxidant markers) levels and peripheral blood lymphocytes were measured in all groups. There were statistically significant differences between the groups for all parameters (P < 0.05). Whole-body irradiation caused a significant increase in blood malondialdehyde, nitrate and nitrite levels. The blood oxidative stress marker levels in irradiated rats that were pretreated with NS and GSH were significantly decreased; however, non-enzymatic antioxidant levels were significantly increased. Also, our results suggest that NS and GSH administration prior to irradiation prevent the number of alpha-naphthyl acetate esterase peripheral blood T lymphocytes from declining. These results clearly show that NS and GSH treatment significantly antagonize the effects of radiation. Therefore, NS and GSH may be a beneficial agent in protection against ionizing radiation-related tissue injury.

 

 

4. (rat study) Oncol Lett. 2010 Sep;1(5):913-924. Epub 2010 Sep 1.

Cancer chemopreventive potential of volatile oil from black cumin seeds, Nigella sativa L., in a rat multi-organ carcinogenesis bioassay.

Salim EI.

 

Source

Research Laboratory of Experimental and Molecular Carcinogenesis, Department of Zoology, Faculty of Science, Tanta University, Tanta 31527, Egypt.

Abstract

Nigella sativa (N. sativa) is a herbal plant of the Ranunculaceae family that has been widely used for various medicinal and nutritional purposes. Volatile oil extracts along with its major constituents, such as thymoquinone, have recently attracted considerable attention for their antioxidant, immunoprotective and antitumor properties. The present study was conducted to assess the chemopreventive potential of crude oils in N. sativa on tumor formation using a well-established rat multi-organ carcinogenesis model featuring initial treatment with five different carcinogens. Post-initiation administration of 1000 or 4000 ppm N. sativa volatile oil in the diet of male Wistar rats for 30 weeks significantly reduced malignant and benign colon tumor sizes, incidences and multiplicities. The treatment also significantly decreased the incidences and multiplicities of tumors in the lungs and in different parts of the alimentary canal, particularly the esophagus and forestomach. Bromodeoxyuridine labeling indices, reflecting cell proliferation were significantly decreased in various organs and lesions after treatment with the two doses of N. sativa. The plasma levels of insulin growth factor, triglycerides and prostaglandin E2 were also altered.The findings show, for the first time, that N. sativa administration exerts potent inhibitory effects on rat tumor development and on cellular proliferation in multiple organ sites. In particular, the ability to significantly inhibit murine colon, lung, esophageal and forestomach tumors was demonstrated in the post-initiation phase, with no evidence of clinical side effects. The mechanisms are likely to be related to suppression of cell proliferation.

 

 

5. Int J Biochem Cell Biol. 2006;38(8):1249-53. Epub 2005 Nov 8.

Thymoquinone: a promising anti-cancer drug from natural sources.

Gali-Muhtasib H, Roessner A, Schneider-Stock R.

Source

Department of Biology, American University of Beirut, Beirut, Lebanon. amro@aub.edu.lb

 

Abstract

There has been growing interest in naturally occurring compounds with anti-cancer potential. Black seed is one of the most extensively studied plants. This annual herb grows in countries bordering the Mediterranean Sea and India. Thymoquinone (TQ) is the bioactive constituent of the volatile oil of black seed. It has been shown to exert anti-neoplastic and anti-inflammatory effects. The molecular pathways of TQ action are not clear. Nevertheless, TQ is known to induce apoptosis by p53-dependent and p53-independent pathways in cancer cell lines. Growth inhibition is associated with induction of cell cycle arrest. TQ also acts on the immune system by modulating the levels of inflammatory mediators. To date, the chemotherapeutic potential of TQ in the clinic has not been tested, but numerous studies have shown its promising anti-cancer effects in animal models. The combination of TQ with clinically used anti-cancer drugs has led to improvements in their therapeutic index and prevents non-tumor tissues from sustaining chemotherapy-induced damage.

 

 

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.

Motaghed M, Al-Hassan FM, Hamid SS.

Source

Oncology and Radiological Science Cluster, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Pulau Pinang, Malaysia.

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 IM thymoquinone. Further analysis using cell cycle assay showed thymoquinone inhibition of breast cancer cell proliferation at minimal dose 25 IM 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 IM thymoquinone for 12 h. Increase in thymoquinone to 50 IM 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.

 

 

7. (see diagram)

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3252704/figure/F2/

 

8. http://www.greenmedinfo.com/article/anti-metastasis-effect-thymoquinone-human-pancreatic-cancer

 

9.

“Antitumor and anti-angiogenesis effects of thymoquinone on osteosarcoma through the NF-KB pathway.”

Abstract Source:

Oncol Rep. 2013 Feb ;29(2):571-8. Epub 2012 Dec 4. PMID: 23232982

Abstract Author(s):

Lei Peng, An Liu, Yue Shen, Hua-Zi Xu, Shi-Zhou Yang, Xiao-Zhou Ying, Wei Liao, Hai-Xiao Liu, Zhong-Qin Lin, Qing-Yu Chen, Shao-Wen Cheng, Wei-Dong Shen

Article Affiliation:

Department of Orthopaedic Surgery, The Second Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang 325000, P.R. China.

Abstract:

Thymoquinone (TQ), the predominant bioactive constituent derived from the medicinal spice Nigella sativa (also known as black cumin), has been applied for medical purposes for more than 2,000 years. Recent studies reported that thymoquinone exhibited inhibitory effects on the cell proliferation of several cancer cell lines. This study was performed to investigate the antitumor and anti-angiogenic effects of thymoquinone on osteosarcoma in vitro and in vivo. Our results showed that thymoquinone induced a higher percentage of growth inhibition and apoptosis in the human osteosarcoma cell line SaOS-2 compared to that of control, and thymoquinone significantly blocked human umbilical vein endothelial cell (HUVEC) tube formation in a dose-dependent manner. To investigate the possible mechanisms involved in these events, we performed electrophoretic mobility shift assay (EMSA) and western blot analysis, and found that thymoquinone significantly downregulated NF-κB DNA-binding activity, XIAP, survivin and VEGF in SaOS-2 cells. Moreover, the expression of cleaved caspase-3 and Smac were upregulated in SaOS-2 cells after treatment with thymoquinone. In addition to these in vitro results, we also found that thymoquinone inhibits tumor angiogenesis and tumor growth through suppressing NF-KB and its regulated molecules. Collectively, our results demonstrate that thymoquinone effectively inhibits tumor growth and angiogenesis both in vitro and in vivo. Moreover, inhibition of NF-KB and downstream effector molecules is a possible underlying mechanism of the antitumor and anti-angiogenic activity of thymoquinone in osteosarcoma.

 

 

10.

Thymoquinone (from the plant Nigella Sativa) has been studied since the 60s for its antioxidant, anti-inflammatory and anticancer effects.

Summary

Abstract Title:

Thymoquinone: potential cure for inflammatory disorders and cancer.

Abstract Source:

Biochem Pharmacol. 2012 Feb 15 ;83(4):443-51. Epub 2011 Oct 10. PMID: 22005518

Abstract Author(s):

Chern Chiuh Woo, Alan Prem Kumar, Gautam Sethi, Kwong Huat Benny Tan

Article Affiliation:

Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore.

Abstract:

Thymoquinone is an active ingredient isolated from Nigella sativa and has been investigated for its anti-oxidant, anti-inflammatory and anticancer activities in both in vitro and in vivo models since its first extraction in 1960s. Its anti-oxidant/anti-inflammatory effect has been reported in various disease models, including encephalomyelitis, diabetes, asthma and carcinogenesis. Moreover, thymoquinone could act as a free radical and superoxide radical scavenger, as well as preserving the activity of various anti-oxidant enzymes such as catalase, glutathione peroxidase and glutathione-S-transferase. The anticancer effect(s) of thymoquinone are mediated through different modes of action, including anti-proliferation, apoptosis induction, cell cycle arrest, ROS generation and anti-metastasis/anti-angiogenesis. In addition, this quinone was found to exhibit anticancer activity through the modulation of multiple molecular targets, including p53, p73, PTEN, STAT3, PPAR-γ, activation of caspases and generation of ROS. The anti-tumor effects of thymoquinone have also been investigated in tumor xenograft mice models for colon, prostate, pancreatic and lung cancer. The combination of thymoquinone and conventional chemotherapeutic drugs could produce greater therapeutic effect as well as reduce the toxicity of the latter. In this review, we summarize the anti-oxidant/anti-inflammatory and anticancer effects of thymoquinone with a focus on its molecular targets, and its possible role in the treatment of inflammatory diseases and cancer.

 

 

11.  Global Veterinaria   Volume 11, Issue 2, 2013, Pages 145-154

Effects of dietary antioxidants supplementation on cellular immune response and evaluation of their antimicrobial activity against some enteric pathogens in goats

Abou-Zeina, H.A.A.a, Ghazy, A.A.a, El-Bayoumy, M.K.a, Dorgham, S.M.b, Khairy, E.A.b, Twfik, H.I.c

a  Department of Parasitology and Animal Diseases, National Research Center, Giza, Egypt

b  Department of Microbiology, National Research Center, Giza, Egypt

c  Department of New Castle, Veterinary Serum and Vaccine Research Institute, Giza, Egypt

View references

Abstract

The present study aimed to investigate the effects of the use of natural antioxidant such as Nigella sativa or black cumin seeds (BCS) and organic multi-nutrient antioxidants, as dietary supplements on cellular immune status and evaluate their antimicrobial effects on some enteric pathogens (E. coli and C. perfringens) in goats. We also aimed to detect certain virulence genes of these pathogens using Multiplex PCR. Fifteen, 4-6 months old Baladi goat kids were divided into three equal groups (n=5). Group A was kept as control and fed the basal diet, group B received basal diet supplemented with crushed BCS at ratio of 2% and group C received basal diet supplemented with the organic multi-nutrient antioxidants; zinc methionine (Zn-Met.) and vitamin E with selenium enriched yeast (Vit E\Se) at levels of 2g\kg of diet. All treatments extended for 120 days. Heparinized blood samples were aseptically collected from all goats at day 0 and once at the end of experimental period for immune cell function studies. The cellular immune responses of experimental animals were assessed by lymphocyte proliferation using XTT kit and phagocytic % & phagocytic index using candida albicans. Fecal samples were collected at day 0 and subsequently at 30 days intervals up to 120 days of experimental period for bacteriological examination and total bacterial counts. Multiplex PCR was carried out for detection of virulent genes F41 and K99 genes for E. coli and alpha, beta and epsilon toxin genes for C. perfringens. The obtained results revealed a significant elevation of lymphocyte and phagocytic activities in groups B and C received antioxidants compared with goats in group A fed the basal diet. Moreover, BCS showed antimicrobial effect against some enteric pathogens by inhibition of the intestinal bacterial counts of E. coli and C. perfringens. Detection of some certain virulent genes for the studied pathogens showed positive results to K99 gene for E. coli and alpha & epsilon toxin genes for C. perfringens type D. In conclusion, dietary supplementation with either N. sativa or multi- nutrient antioxidants (Zn-Met. and Vit E\Se) can be used to provide potent immune cell function in goats. Moreover, N. sativa had proved to have antibacterial effect against some enteric pathogens.

 

 

12. effect on memory study:

Journal of Ethnopharmacology

Volume 148, Issue 3, 30 July 2013, Pages 780–786

 

The effect of Nigella sativa Linn. seed on memory, attention and cognition in healthy human volunteers

* Muhammad Shahdaat Bin Sayeeda, b, , ,

*  Md. Asaduzzamanb, c,

*  Helal Morshedd,

*  Md. Monir Hossaina,

*  Mohammad Fahim Kadirb, c,

*  Md. Rezowanur Rahmanc

* a Department of Clinical Pharmacy and Pharmacology, University of Dhaka, Bangladesh

* b Department of Pharmacy, University of Asia Pacific, Dhanmondi, Dhaka, Bangladesh

* c Department of Pharmaceutical Technology, University of Dhaka, Bangladesh

* d Department of Pharmaceutical Chemistry, University of Dhaka, Bangladesh

 

Abstract

Background

Experimental evidences have demonstrated that Nigella sativa Linn. seed (NS) has positive modulation effects on aged rats with memory impairments, prevents against hippocampal pyramidal cell loss and enhances consolidation of recall capability of stored information and spatial memory in rats. NS has neuroprotective, nephroprotective, lung protective, cardioprotective, hepatoprotective activities as established by previous studies on animals. Several clinical trials with NS on human have also demonstrated beneficial effect.

Aim of the study

The present study was designed to investigate the effects of NS on memory, attention and cognition in healthy elderly volunteers. Furthermore, safety profile of NS was assessed during the nine-week study period.

Methods

Forty elderly volunteers were recruited and divided randomly into group A and group each consisting of 20 volunteers. The treatment procedure for group A was 500 mg NS capsule twice daily for nine weeks and Group B received placebo instead of NS in the similar manner. All the volunteers were assessed for neuropsychological state and safety profile twice before treatment and after nine weeks. The neuropsychological tests were logical memory test, digit span test, Rey-Osterrieth complex figure test, letter cancellation test, trail making test and stroop test. Safety profile was assessed by measuring biochemical markers of Cardiac (total cholesterol, triglycerides and high density lipoprotein cholesterol, very low density lipoprotein, low density lipoprotein cholesterol, creatine kinase-MB); Liver (aspartate aminotransferase, alanin aminotransferase, alkaline phosphatase, total protein, albumin, bilirubin) and Kidney (creatinine and blood urea nitrogen) through using commercial kits.

Results

There was significant difference (p<0.05) in the score of logical memory test-I and II, total score of digit span, 30 min delayed-recall, percent score in Rey-Osterrieth complex figure test, time taken to complete letter cancellation test, time taken in trail making test-A and test-B, score in part C of stroop test due to ingestion of NS for nine weeks. There were not statistically significant changes (p>0.05) in any of the biochemical markers of cardiac, liver, kidney function during this nine-week study period.

Conclusions

The current study demonstrates the role of NS in enhancing memory, attention and cognition. Therefore, whether NS could be considered as potential food supplement for preventing or slow progressing of Alzheimer disease needs further investigations. However, study with Alzheimer’s patients with large population size for longer period of time is recommended before using NS daily and extensive phytochemical investigations are recommended for novel drug discovery from NS for treating cognitive disorders.

 

 

13. European Food Research and Technology

May 2012, Volume 234, Issue 5, pp 833-844

Antiradical and antimicrobial properties of cold-pressed black cumin and cumin oils

* Mohamed Fawzy Ramadan,

*  Mohsen Mohamed Selim Asker,

*  Mounier Tadros

Abstract

Cold-pressed black cumin seed oil (BCSO) and cumin seed oil (CSO) were evaluated for their fatty acid profiles, phytosterol and tocopherol contents, antiradical properties and inhibition of microbial growth. The main fatty acids in BCSO were linoleic followed by oleic and palmitic acids. Petroselinic acid (C18:1n-12) was the main fatty acid in CSO, while linoleic acid was the second major unsaturated acid. Six sterol compounds were measured in BCSO and CSO, wherein the sterol marker was β-sitosterol. α-Tocopherol constituted 45% of tocopherols in BCSO, while β-tocopherol was the main component in CSO. BCSO and CSO oils had higher antiradical action against DPPH· and galvinoxyl radicals than virgin olive oil.

 

Antimicrobial properties of BCSO and CSO were studied, and the results revealed that CSO inhibited the growth of all microorganisms tested, while BCSO inhibited the growth of all microorganisms tested except A. niger and A. flavus.  BCSO and CSO had a drastic effect on the biosynthesis of protein and lipids in cells of B. subtilis.
14.  Androgen Receptor and E2F-1Targeted Thymoquinone Therapy for Hormone-Refractory Prostate Cancer

1. Ahmed O. Kaseb1,

2.  Kannagi Chinnakannu2,

3.  Di Chen3,4,

4.  Arun Sivanandam2,

5. Sheela Tejwani1,

6.  Mani Menon2,

7.  Q. Ping Dou3,4, and

8.  G. Prem-Veer Reddy2,3,4

+Author Affiliations

1. 1Department of Hematology/Oncology and 2Vattikuti Urology Institute, Henry Ford Hospital; 3Barbara Ann Karmanos Cancer Institute; and 4Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan

1. Requests for reprints:

2. G. Prem-Veer Reddy, Vattikuti Urology Institute, Henry Ford Health System, One Ford Place, 2D, Detroit, MI 458202. Phone: 313-874-5991; E-mail: Preddy1@hfhs.org.

 

Abstract

Relapse of prostate cancer after androgen ablation therapy is hormone-refractory, with continued tumor growth being dependent on the androgen receptor (AR). E2F-1, a regulator of cell proliferation and viability, reportedly plays a role in the development of hormone-refractory prostate cancer. Thymoquinone is a component of Nigella sativa, an herb used for thousands of years for culinary and medicinal purposes in Asian and Middle Eastern countries and has been reported to have an antineoplastic effect both in vitro and in vivo.

 

We observed that thymoquinone inhibited DNA synthesis, proliferation, and viability of cancerous (LNCaP, C4-B, DU145, and PC-3) but not noncancerous (BPH-1) prostate epithelial cells by down-regulating AR and E2F-1. In LNCaP cells, this was associated with a dramatic increase in p21Cip1, p27Kip1, and Bax.

 

Thymoquinone blunted progression of synchronized LNCaP cells from G1 to S phase, with a concomitant decrease in AR and E2F-1 as well as the E2F-1-regulated proteins necessary for cell cycle progression. In a xenograft prostate tumor model, thymoquinone inhibited growth of C4-2B–derived tumors in nude mice. This in vivo suppression of tumor growth, as with C4-2B cell growth in culture, was associated with a dramatic decrease in AR, E2F-1, and cyclin A as determined by Western blot of tissue extracts. Tissue immunohistochemical staining confirmed a marked reduction in E2F-1 and showed induction of apoptosis on terminal deoxyribonucleotidyl transferase–mediated dUTP nick end labeling assay. These findings show that thymoquinone suppresses the expression of AR and E2F-1 necessary for proliferation and viability of androgen-sensitive as well as androgen-independent prostate cancer cells both in vitro and in vivo and, moreover, produced no noticeable side effects in mice.

 

We conclude that thymoquinone, a naturally occurring herbal product, may prove to be effective in treating hormone-sensitive as well as hormone-refractory prostate cancer. Furthermore, because of its selective effect on cancer cells, we believe that thymoquinone can also be used safely to help prevent the development of prostate cancer. [Cancer Res 2007;67(16):7782–8]

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