Abstract 5518: BPM 31510 exposure alters fluidity and molecular organization of cancer cell membranes, influencing signaling and cell fate decisions

Abstract

Abstract The dynamic state of membranes impinges on pathways critical for cancer cell survival or death while influencing cancer cell metabolism. Here in, we investigated the effects of BPM 31510, a proprietary ubidecarenone formulation, on temporal alterations in membrane adaptation, proteomic and lipidomic reorganization, initiation of key apoptotic signaling pathways, bioenergetic integration, as well as cell fate decision processes in in vitro models of representative cancers. This approach was harvested to decipher a systems wide understanding of BPM 31510's effects on various human cancer cell lines (prostate, pancreatic, skin, breast and ovarian ) as well as effect on representative control cell lines. BPM 31510 exposure in vitro resulted in a stochastic shift in membrane fluidity in various cancer cell lines. Global untargeted shotgun lipidomics and proteomics revealed selective lipidomic and protein shifts in a temporal manner across various cancer lines resultant from BPM 31510 exposure. Berg informatics suite comprising of Bayesian artificial intelligence systems engineering framework linked specific pivot lipid molecular species and proteins to the action of BPM 31510 based on dynamic time course experiments and biological endpoints including cellular metabolism and cell fate (apoptosis) across cancer cell lines. Thus, the data presented within demonstrate that BPM 31510 affects the cancer cell biomembrane structure, membrane lipid reorganization with potential to influence intracellular signaling, cell fate decision making processes and metabolism. The systems approach described within provides novel insight into the pleiotropic effects of BPM 31510 on cancer cells. Citation Format: Michael Kiebish, Sumit Garg, Vivek Vishnudas, Fei Gao, Min Du, Sirisha Dhavala, Katerina Krumova, Leonardo Rodriguez, Shen Luan, Viatcheslav R. Akmaev, Rangaprasad Sarangarajan, Niven R. Narain. BPM 31510 exposure alters fluidity and molecular organization of cancer cell membranes, influencing signaling and cell fate decisions. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5518. doi:10.1158/1538-7445.AM2014-5518