NOTCH-1 DOWN REGULATION CONTRIBUTES TO GENISTEIN INDUCED GROWTH INHIBITION AND APO-PTOSIS IN BXPC-3 PANCREATIC CANCER CELLS.

Abstract

Background: Notch signaling plays a critical role in maintaining the balance between cell proliferation, differentiation, and apoptosis. Hence, perturbation in Notch signaling may contribute to tumorigenesis. It has been reported that Notch signaling is involved in pancreas organ development. Recent evidence also suggests that the Notch signaling pathway is involved in pancreatic cancer cell survival. Therefore, down-regulation of Notch signaling may be a novel approach for pancreatic cancer therapy. Genistein, a component of soy, has been reported to down regulate many genes that control cell survival, and also up-regulate genes which promote apoptosis of BxPC3 pancreatic cancer cells in vitro. However, there is no report, to date, whether genistein could also down regulate Notch-1 signaling which may lead to the induction of cell growth inhibition and apoptosis in pancreatic cancer cells. We therefore hypothesize that deregulation of Notch-1 signaling contributes to genistein-induced cell growth inhibition and apoptosis in pancreatic cancer cells. Methods: BxPC-3 pancreatic cancer cells were cultured and exposed to various concentrations of genistein. Subsequently, cell growth inhibition and apoptosis was measured using MTT and Apoptosis ELISA assay, respectively. Notch-1 expression was determined by Real time RT-PCR and Western blot analysis. Results: Genistein inhibited cell growth and also induced apoptosis in BxPC3 cells in a dose- and time-dependent manner. Notch-1 expression was down regulated by genistein and these results were correlated well with the degree of apoptosis induced by genistein. Conclusions: Our results demonstrate, for the first time, that Notch-1 signaling pathway may play important roles during genistein-induced cell growth inhibition and apoptosis in BxPC3 pancreatic cancer cells. These results suggest that down regulation of Notch signaling by genistein could be a novel strategy for the treatment of pancreatic cancer.