Abstract 2455: Differences in dynamic modulation of CoQ10 redox status and intracellular localization between non-disease and cancer cell lines

Abstract

Abstract Although it is well recognized that Coenzyme Q10 (CoQ10) is present in all cellular membrane structures, its effects on cellular functions other than mitochondrial regulation is poorly understood. The present study was aimed at gleaning insights into effect on CoQ10 on sub-cellular metabolism, regulation of the redox status, as well as gene regulation. A series of fluorescent probes were developed with the ability to report on the consequence of specific biological events in which CoQ10 was involved. The probes constituted fluorescently labeled CoQ10 analogues designed to track the distribution, biochemical and redox behaviour of CoQ10 in a non-invasive manner providing real time information in live cells. Compartmentalization of fluorescent labeled CoQ10 probe incorporated within BPM 31510 liposomal formulation was characterized in human derived primary non-disease and cancer cell lines. Cellular distribution of the fluorescent CoQ10 varied depending upon cell type. The fluorescent CoQ10 probes were designed and utility to provide a time resolved assessment on the redox state of CoQ10 in whole cells and organelles as a measure of the cell's overall and intracellular location specific metabolic micro-environments. The ratio of reduced and oxidized form of fluorescent CoQ10 was also examined in relation to ROS production in cancer cells. The overall results describes the presence of a constant redox flux influencing the redox state of CoQ10 within cancer and normal cells with significant variation depending on cell type and disease status. Citation Format: Katerina Krumova, Sumit Garg, Sirisha Dhavala, Vivek K. Vishnudas, Michael A. Kiebish, Rangaprasad Sarangarajan, Niven R. Narain. Differences in dynamic modulation of CoQ10 redox status and intracellular localization between non-disease and cancer cell lines. [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 2455. doi:10.1158/1538-7445.AM2015-2455