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Nigella Sativa

Jacob Schor ND FABNO

July 2009

Denver's main mosque is located just down the road from our office.  Directly across the street is a small grocery catering to mosque visitors.  They sell relatively hard to find foods, a butcher shop offering Halal meat, and shelves stocked with foodstuffs unique to faraway places.  We shop there occasionally, mostly for sesame tahini, olives and odd impulse purchases.  I recently returned home with a jar of grape ‘molasses’ that appears to be thick syrup made from boiled down grape juice.

 

Every year during the Fast of Ramadan the store stocks and sells a tonic made from Nigella sativa seeds, commonly called black cumin seed that is said to cleanse the body.  This isn’t actually cumin seed.   Nigella sativa seed goes by a range of different and pretty much all misleading names: it is called fennel flower, nutmeg flower, Roman coriander, blackseed, black caraway, or black onion seed. This confusion is probably due to nigella being such a new spice in the western world that at this point there isn’t an agreed upon translation.

The prophet Muhammad is quoted as saying that the black seed can heal every disease—except death.

Nigella seeds are considered as something of a panacea in the Middle East and Southeast Asia and used to treat a range of conditions including asthma, bronchitis, rheumatism and related inflammatory diseases, to increase milk production in nursing mothers, to promote digestion and to fight parasitic infections. Nigella oil has been used to treat skin conditions such as eczema and boils and to treat cold symptoms.

We are interested in nigella because of a series of papers published in recent years suggesting it may be of use in treating cancer. 

The first of these papers was published in 1998 in Cancer Research.

The authors reported on experiments using both crude extracts and refined oils obtained from nigella seed, testing the effect on human cancer cells.  The crude gum had no effect but the purified extract thymoquinone (TQ) and dithymoquinone (DIM) both effectively killed all the cancer cell lines they were tested on.  Even cell lines that had developed multi-drug resistance (MDR) to doxorubicin and etoposide were sensitive.

The second paper of interest was published in 2005.  Irish researchers reported their results testing extracts of Nigella sativa on lung cancer, cancer of the larynx, colon cancer and pancreatic cancer cell lines.  The extracts caused cancer cell death by both apoptosis and necrosis in a dose and time dependent manner.

A June 2009 paper is the most interesting.  This paper tells us that thymoquinone, the compound extracted from Nigella sativa sensitizes pancreatic cancer cells to chemotherapy drugs both in test tube experiments and in animals.

In test tube experiments, pretreatment of pancreatic cancer cells with thymoquinone for 48 hours and then treating them with either gemcitabine or oxaliplatin, resulted in 60% to 80% growth inhibition compared to 15% to 25% when either drug was used alone.

The thymoquinone increased chemotherapy’s  killing of pancreatic cancer cells by decreasing nuclear factor-kappaB.  Usually chemotherapy activates NF-kappaB in pancreatic cancer cells.  Because thymoquinone decreased NF-kappaB in the cancer cells were more sensitive to chemotherapy. Furthermore, this paper tells us that, combining thymoquinone with gemcitabine and/or oxaliplatin is much more effective at killing cancer cells than either drug is alone.

References:

Worthen DR, et al. The in vitro anti-tumor activity of some crude and purified components of blackseed, Nigella sativa L. Anticancer Res. 1998 May-Jun;18(3A):1527-32.

   

Rooney S, Ryan MF. Effects of alpha-hederin and thymoquinone, constituents of Nigella sativa, on human cancer cell lines.  Anticancer Res. 2005 May-Jun;25(3B):2199-204.

   

Banerjee S, et al. Antitumor Activity of Gemcitabine and Oxaliplatin Is Augmented by Thymoquinone in Pancreatic Cancer.  Cancer Res. 2009 Jun 23.

Abstracts:

 

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.

    Worthen DR, Ghosheh OA, Crooks PA.

    Natural Products Chemistry Laboratory, Tobacco and Health Research Institute, Lexington, KY 40536, USA.

    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.

 

Anticancer Res. 2005 May-Jun;25(3B):2199-204.

    Effects of alpha-hederin and thymoquinone, constituents of Nigella sativa, on human cancer cell lines.

    Rooney S, Ryan MF.

    Department of Zoology, University College Dublin, Belfield, Dublin 4, Ireland.

    The separate effects of alpha-hederin and thymoquinone, the two principal bioactive constituents of Nigella sativa, on four human cancer cell lines [A549 (lung carcinoma), HEp-2 (larynx epidermoid carcinoma), HT-29 (colon adenocarcinoma) and MIA PaCa-2 (pancreas carcinoma)] were investigated. Alpha-hederin was also examined as a pro-drug. Each assessment quantified both cytotoxic and apoptotic/necrotic effects. Alpha-hederin and thymoquinone separately induced a dose- and time-dependent effect on the cell lines tested. HEp-2 cells were the most sensitive, exhibiting apoptosis with a higher incidence following thymoquinone treatment. Pre-treatment of cells with alpha-hederin, followed by thymoquinone or cisplatin, did not enhance the cytotoxicity or apoptosis induced by either drug. So, the membrane-perforating properties associated with saponins, here represented by alpha-hederin, enhance neither cytotoxicity nor apoptosis of these cancer cells.

    PMID: 16158964

Cancer Res. 2009 Jun 23. [Epub ahead of print]

    Antitumor Activity of Gemcitabine and Oxaliplatin Is Augmented by Thymoquinone in Pancreatic Cancer.

    Banerjee S, Kaseb AO, Wang Z, Kong D, Mohammad M, Padhye S, Sarkar FH, Mohammad RM.

    Department of Pathology and Division of Hematology and Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan; and Department of Gastrointestinal Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas.

    Previous studies have shown biological activity of thymoquinone, an active compound extracted from Nigella sativa, in pancreatic cancer cells; however, preclinical animal studies are lacking. Here, we report, for the first time, the chemosensitizing effect of thymoquinone to conventional chemotherapeutic agents both in vitro and in vivo using an orthotopic model of pancreatic cancer. In vitro studies revealed that preexposure of cells with thymoquinone (25 micromol/L) for 48 h followed by gemcitabine or oxaliplatin resulted in 60% to 80% growth inhibition compared with 15% to 25% when gemcitabine or oxaliplatin was used alone. Moreover, we found that thymoquinone could potentiate the killing of pancreatic cancer cells induced by chemotherapeutic agents by down-regulation of nuclear factor-kappaB (NF-kappaB), Bcl-2 family, and NF-kappaB-dependent antiapoptotic genes (X-linked inhibitors of apoptosis, survivin, and cyclooxygenase-2). As shown previously by our laboratory, NF-kappaB gets activated on exposure of pancreatic cancer cells to conventional chemotherapeutic agents; interestingly, thymoquinone was able to down-regulate NF-kappaB in vitro, resulting in chemosensitization. In addition to in vitro results, here we show for the first time, that thymoquinone in combination with gemcitabine and/or oxaliplatin is much more effective as an antitumor agent compared with either agent alone. Most importantly, our data also showed that a specific target, such as NF-kappaB, was inactivated in animal tumors pretreated with thymoquinone followed by gemcitabine and/or oxaliplatin. These results provide strong in vivo molecular evidence in support of our hypothesis that thymoquinone could abrogate gemcitabine- or oxaliplatin-induced activation of NF-kappaB, resulting in the chemosensitization of pancreatic tumors to conventional therapeutics. [Cancer Res 2009;69(13):5575-83].

    PMID: 19549912