Abstract 1736: Mitochondrial priming of apoptotic machinery in pancreatic cancer by BPM 31510 to enhance efficacy of chemotherapy.

Abstract

Abstract Recent evidence suggests that the cytotoxic effects of chemotherapy, specifically in cancer cells is a consequence of “pre-treatment priming” event wherein exposure to the chemotherapeutic agents pushes the cancer cells beyond an apoptotic threshold to effectuate cell death. (Letai, A et. al, Science. 2011 Nov 25;334 (6059) BPM 31510 is a ubidecarenone containing proprietary formulation that effectuates a metabolic switch from glycolysis towards enhanced mitochondrial oxidative phosphorylation resulting in the recapitulation of apoptosis in cancer. The current study was aimed at investigating whether pretreatment with BPM 31510 results in mitochondrial priming, thereby augmenting the cytotoxic effect of standard of care chemotherapeutic agents. The human derived pancreatic cancer cell line Mia-Paca-2 was subjected to either (a) pretreatment with BPM 31510 followed by co-treatment with gemcitabine or (b) co-treatment with BPM 31510 and gemcitabine. BPM 31510 exposure resulted in decreased cell proliferation rates that were significantly higher than gemcitabine alone in Mia-Paca-2 cell line. Pre-treatment with BPM 31510 augmented the cytotoxic potential of gemcitabine, a phenomenon that was also observed in the co-treatment regimen. In vivo pancreatic cancer model using Mia-Paca-2 cell lines were developed to further investigate the priming effect of BPM 31510. Results demonstrate that 1-week and 2-week pretreatment with intravenous BPM 31510 followed by gemcitabine results in improved survival in the pancreatic cancer model compared to the co-treatment regimen. The data demonstrates that addition of BPM 31510 synergizes the cytotoxic effect of gemcitabine in pancreatic cancer. In addition, pretreatment with BPM 31510 followed by gemcitabine treatment is associated with improved survival. Taken together, the data suggest that BPM 31510 may be a viable mitochondrial priming agent to sensitize cancer cells to the cytotoxic effects of gemcitabine in pancreatic cancer. Citation Format: Niven R. Narain, Tony E. Walshe, Arleide Lee, Rakib Ouro-Djoba, Lucia Mauro, Adel Yunis, Vivek K. Vishnudas, Rangaprasad Sarangarjan, Joaquin J. Jimenez. Mitochondrial priming of apoptotic machinery in pancreatic cancer by BPM 31510 to enhance efficacy of chemotherapy. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1736. doi:10.1158/1538-7445.AM2013-1736