Chemotherapy for pancreatic cancer possibly enhanced with Black Seed ingredient

Researchers at the Department of Pathology and Division of Hematology and Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, and the Department of Gastrointestinal Medical Oncology, University of Texas M. D. Anderson Cancer Center note that Thymoquinone, an active compound extracted from Nigella sativa (Black Seed) battles pancreatic cancer cells; however, preclinical animal studies are lacking.

Here, they report, for the first time, the chemo-sensitizing effect of Thymoquinone to conventional chemotherapeutic agents both in vitro and in vivo using an orthotopic model of pancreatic cancer (human pancreatic cancer was implanted in the animals in the same region it commonly occurs in the human body). In vitro studies revealed that exposing the pancreatic cancer cells to Thymoquinone (25 micromol/L) for 48 hours before exposing them to chemo improved the cancer fighting power of commonly used chemotherapeutic drugs. The cells were treated with the Black Seed ingredient followed by the drugs gemcitabine (Gemzar) or oxaliplatin. Pretreatment with Black Seeds Thymoquinone before chemo resulted in 60% to 80% growth inhibition compared with 15% to 25% when gemcitabine or oxaliplatin was used alone.

Technical info; the researchers 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 chemo-sensitization. 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.

In the second part of the study and most importantly, their 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 their hypothesis that Thymoquinone could abrogate gemcitabine- or oxaliplatin-induced activation of NF-kappaB, resulting in the chemo-sensitization of pancreatic tumors to conventional therapeutics. The study is published online ahead of print on June 23rd, 2009 in the journal Cancer Research.