Abstract
Abstract Pancreatic cancer is a devastating disease with a poor prognosis. The American Cancer Society's estimates for pancreatic cancer in the United States for 2014 are about 46,420 new cases of pancreatic cancer and about 39,590 deaths from pancreatic cancer. There remains a clear need for effective mechanism-based approaches that can achieve long-term improvements in the management pancreatic cancer. While natural products are well recognized as sources of drugs for various diseases including cancer, very few studies systematically explored the role of natural products for their potential preventive/therapeutic benefit in pancreatic cancer. Although several studies have examined the effect of flavonoids, there are no studies examining how biochanin-A or atorvastatin regulates pancreatic cancer cells. We investigated the cell proliferation studies in pancreatic cancer cell lines, AsPC-1 and MiaPaCa-2. Interestingly, we observed that by combination of treatment of Biochanin-A and atorvastatin significantly decreased the viability of AsPC-1 and MiaPaCa-2 cells. Several studies have been demonstrated the STAT3 play an important roll in the progression cancer pathogenesis in various cancers. We examined the STAT3 expression in pancreatic cell line, PANC-1 in biochanin-A or atorvastatin or in combination treatments and observed 95% decrease in the phosphorylation of STAT3 observed. Similarly the combination drug treatment employing biochanin A and atorvastatin decreased activation of Akt in AsPC-1 cell line. The decreased cell viability in AsPC-1 cell line involved increased induction of apoptosis with combination treatment and this evidence was further strengthened by increased PARP cleavage in combination treated cells. Further studies will delineate the mechanism of signaling arrested by the combination of drugs, Biochanin-A and atorvastatin in pancreatic cells with the possibility for uncovering improved therapeutic strategies to overcome the effectiveness to treat pancreatic cancer patients. Citation Format: Alok Bhushan, Ponniah Selvakumar, Satya Murthy Tadinada, James C.K. Lai. The dietary isoflavone biochanin-A in combination with atorvastatin induces cell cycle arrest and apoptosis in human pancreatic cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2538. doi:10.1158/1538-7445.AM2015-2538
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