Abstract 4193: Biochanin A in pancreatic cancer

Vilas Desai; Satya Murthy Tadinada; James C K Lai; Alok Bhushan

doi:10.1158/1538-7445.AM2018-4193

Pancreatic cancer, with its dismally low survival rate (<5%), is one of the most aggressive forms of cancer and is the fourth leading cause of cancer-related deaths in the U.S. Gemcitabine, the first-line drug approved by the FDA, has been marginally effective as it improves survival by only six months. Epidemiologic studies have implicated a role for dietary isoflavones in lowering the incidence of different cancers in the Asian population. Isoflavones such as genistein, biochanin A and daidzein have been tested for their anticancer potential in different cancers; however, the clastogenic effect associated with genistein limits its therapeutic potential. Primarily used in management of hyperlipidemia and cardiovascular diseases, statins have been documented to exert antiproliferative effects. We hypothesized that a combination treatment of biochanin A and atorvastatin exerts enhanced anticancer effects on pancreatic cancer cells viz. AsPC1, PANC-1 and MIAPaCa-2. Our studies showed a decrease in cell viability on combination drug treatment with differential effects on mitogenic and cell signaling pathways in the cell lines investigated. In PANC-1 cells, biochanin A and atorvastatin combination treatment decreased invasiveness, dampened the expression of activated STAT3, and critical mediators of cell cycle progression. We also observed the involvement of enhanced proapoptotic effect of the combination treatment in AsPC-1 cell line and potential cell cycle arrest phenomenon in PANC-1 cells. Cell metabolism studies using seahorse XFp analyzer showed an increase in mitochondrial respiration and a decrease in glycolytic activity on combination treatment. Further, the XF-Plasma Membrane Permeabilizer (XF-PMP) assay used to evaluate the mitochondrial ETC complex activity showed a complete impairment of complex I and II (prominently), with MIAPaCa-2 being more susceptible to the combination treatment than AsPC1 and PANC-1. Together, the combination treatment-induced effects on pancreatic cancer cell lines may have potential implications in developing novel and improved therapies for the treatment of pancreatic cancer. Citation Format: Vilas Desai, Satya Murthy Tadinada, James C K Lai, Alok Bhushan. Biochanin A in pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4193.

Abstract 4193: Biochanin A in pancreatic cancer

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