Oncology Medical News about pancreatic cancer;antitumor activity;Gemcitabine;Oxaliplatin;Thymoquinone

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Antitumor activity of gemcitabine and oxaliplatin is augmented by thymoquinone in pancreatic cancer
Cancer Research, 07/07/09

Banerjee S et al. - In a study to examine the chemosensitizing effect of thymoquinone to conventional chemotherapeutic agents both in vitro and in vivo using an orthotopic model of pancreatic cancer (PCa), the results provide strong in vivo molecular evidence in support of the hypothesis that thymoquinone could abrogate gemcitabine- or oxaliplatin-induced activation of nuclear factor-κB (NF-κB), resulting in chemosensitization of pancreatic tumors to conventional therapeutics.

Methods

Previous studies have shown biological activity of thymoquinone in PCa cells; however, preclinical animal studies are lacking.

Results

In vitro studies revealed that preexposure of cells with thymoquinone (25 μmol/L) for 48 hr followed by gemcitabine or oxaliplatin resulted in 60% to 80% growth inhibition vs 15% to 25% when gemcitabine or oxaliplatin was used alone.
Thymoquinone could potentiate the killing of PCa cells induced by chemotherapeutic agents by down-regulation of NF-κB, Bcl-2 family, and NF-κB-dependent antiapoptotic genes (X-linked inhibitors of apoptosis, survivin, and cyclooxygenase-2).
NF-κB gets activated on exposure of PCa cells to conventional chemotherapeutic agents; thymoquinone was able to down-regulate NF-κB in vitro, resulting in chemosensitization.
It was also shown that thymoquinone in combination with gemcitabine and/or oxaliplatin is much more effective as an antitumor agent vs either agent alone.
These data showed that a specific target, such as NF-κB, was inactivated in animal tumors pretreated with thymoquinone followed by gemcitabine and/or oxaliplatin.

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