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Vitamin E Succinate (VES, α -tocopheryl succinate) is the most potent analog of Vitamin E that selectively induces apoptosis in cancer cells by modulating the expression of Bcl-2 family proteins. VES has been studied extensively as a chemopreventive, chemotherapeutic and chemosensitizing agent in various cancers types. However, there is limited data on the role of VES in pancreatic cancer. Pancreatic cancer is the number four cancer killer in the US and about 32,000 new cases are reported every year. The five year survival rate is only 5%. In this study, we investigated the effects of VES in three pancreatic cancer cell lines, COLO-357, PANC-1 and ASPC-1. We assessed the synergistic growth inhibitory effect of VES along with two known cytotoxic drugs, Etoposide and Gemcitabine. Cells were treated with varying concentrations (5 μM to 100 μM) of VES alone or in combination with Etoposide or Gemcitabine for different time periods. VES inhibited the cell proliferation of all the three pancreatic cancer cell lines in a time and dose dependant manner. Induction of apoptosis was evident in COLO-357 cells as determined by DNA fragmentation, PARP cleavage and increase in sub-G1 cells post treatment. We have also demonstrated that VES synergistically inhibits the cell growth in combination with 80 μM etoposide or 0.5 μg/ml Gemcitabine. In ASPC-1 cells, we also observed a dose dependent decrease in the expression of Bcl-XL in response to VES. This study demonstrates that (a)VES induces apoptosis in pancreatic cancer cell lines (b) VES synergistically inhibits the growth of pancreatic cancer cells in combination with cytotoxic drugs Etoposide or Gemcitabine and (c) VES down regulates the expression of antiapoptotic protein Bcl-XL in ASPC-1 cells.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA