Black Cumin seeds and Pancreatic Cancer

Dr. Weeks’ Comment: Black cumin seed is the powerful anti-cancer and anti-inflammatory food which is the cornerstone of the revolution in nutrition – eat the seed. Thymoquinone “TQ” is an active ingredient in black cumin seed. Here we see that black cumin seed is helpful even against the dreaded pancreatic cancer.

“…Present TQ analogs exhibit superior anti-proliferative activity, excellent chemo-sensitizing activity against pancreatic cancer in vitro and in combination with Gemcitabine…”

“…Consequently, these results provide important insights into thymoquinone as an antimetastatic agent for the treatment of human pancreatic cancer…”

“…Overall, TQ has potential for the development of novel therapies against pancreatic cancer…”

1.

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.

Yusufi M1, Banerjee SMohammad MKhatal SVenkateswara Swamy KKhan EMAboukameel ASarkar FHPadhye S.

Abstract

Thymoquinone (TQ), isolated from the seeds of Nigella sativa, show moderate efficacy against pancreatic cancer. 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.

2.

Yao Xue Xue Bao.2011 Aug;46(8):910-4.

[Anti-metastasis effect of thymoquinone on human pancreatic cancer].

[Article in Chinese]

Wu ZH1, Chen ZShen YHuang LLJiang P.

Abstract

Recent studies reported that thymoquinone (TQ), a component derived from the medicinal spice Nigella sativa (also called black cumin), exhibited inhibitory effects on cell proliferation of many cancer cell lines. This study was performed to investigate the anti-metastatic effect of thymoquinone on the pancreatic cancer in vitro and in vivo. The results showed that thymoquinone suppressed the migration and invasion of Panc-1 cells in a does-dependent manner. To investigate the possible mechanisms involved in these events, Western blotting analysis was performed, and found that thymoquinone significantly down-regulates NF-kappaB and MMP-9 in Panc-1 cells. In addition, metastatic model simulating human pancreatic cancer was established by orthotropic implantation of histologically intact pancreatic tumor tissue into the pancreatic wall of nude mice. And administration of thymoquinone significantly reduced tumor metastasis compared to untreated control. Furthermore, the expression of NF-kappaB and MMP-9 in tumor tissues was also suppressed after treatment with thymoquinone. Taken together, the results indicate that thymoquinone exerts anti-metastatic activity on pancreatic cancer both in vitro and in vivo, which may be related to down-regulation of NF-kappaB and its regulated molecules such as MMP-9 protein. Consequently, these results provide important insights into thymoquinone as an antimetastatic agent for the treatment of human pancreatic cancer.

3.

Mol Cancer Ther.2010 May;9(5):1419-31. doi: 10.1158/1535-7163.MCT-10-0075. Epub 2010 Apr 27.

Effects of thymoquinone in the expression of mucin 4 in pancreatic cancer cells: implications for the development of novel cancer therapies.

Torres MP1, Ponnusamy MPChakraborty SSmith LMDas SArafat HABatra SK.

Abstract

Pancreatic cancer is one of the most lethal cancers in the world, as it continues to be resistant to any therapeutic approaches. The high molecular weight glycoprotein mucin 4 (MUC4) is aberrantly expressed in pancreatic cancer and contributes to the regulation of differentiation, proliferation, metastasis, and the chemoresistance of pancreatic cancer cells. The absence of its expression in the normal pancreatic ductal cells makes MUC4 a promising target for novel cancer therapeutics. Natural products have been widely investigated as potential candidates in cancer therapies, and thymoquinone (TQ), extracted from the seeds of Nigella sativa, has shown excellent antineoplastic properties in some systems. In the present study, we evaluated the effect of TQ on pancreatic cancer cells and specifically investigated its effect on MUC4 expression. The MUC4-expressing pancreatic cancer cells FG/COLO357 and CD18/HPAF were incubated with TQ, and in vitro functional assays were done. The results obtained indicate that treatment with TQ downregulated MUC4 expression through the proteasomal pathway and induced apoptosis in pancreatic cancer cells by the activation of c-Jun NH(2)-terminal kinase and p38 mitogen-activated protein kinase pathways. In agreement with previous studies, the decrease in MUC4 expression correlated with an increase in apoptosis, decreased motility, and decreased migration of pancreatic cancer cells. MUC4 transient silencing studies showed that c-Jun NH(2)-terminal kinase and p38 mitogen-activated protein kinase pathways are activated in pancreatic cancer cells, indicating that the activation of these pathways by TQ is directly related to the MUC4 downregulation induced by the drug. Overall, TQ has potential for the development of novel therapies against pancreatic cancer.

4.

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.

Banerjee S1, Azmi ASPadhye SSingh MWBaruah JBPhilip PASarkar FHMohammad RM.

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.

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.

5.

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.

Chehl N1, Chipitsyna GGong QYeo CJArafat HA.

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).

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.

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Dr. Weeks’ Comment: Black cumin seed is the powerful anti-cancer and anti-inflammatory food which is the cornerstone of the revolution in nutrition – eat the seed. Thymoquinone “TQ” is an active ingredient in black cumin seed. Here we see that black cumin seed is helpful even against the dreaded pancreatic cancer. “…Present TQ analogs exhibit…
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