Abstract
Abstract African American (AA) patients with prostate cancer (PCa) respond poorly to current therapy compared to Caucasian American (CA) patients. Although underlying mechanisms are not clearly defined, mitochondria dysfunction is a key reason for PCa disparity. We observed that glycolytic pathway inhibitor dichloroacetate (DCA) inhibited cell proliferation in both AA PCa cells (AA cells) and CA PCa cells (CA cells). CA cells were arrested at G1 and G2/M phases whereas S-phase arrest was observed in AA cells. AA cells showed resistance to cell death upon DCA exposure in spite of higher caspase activation than in CA cells. AA cells possess reduced level of reactive oxygen species (ROS) and mitochondrial membrane potential (mtMP) compared to CA cells. DCA induced cellular and mitochondrial ROS in AA cells but were unchanged in CA cells. DCA upregulated the levels of mtMP in both cell types. DCA enhanced taxol-induced cell death only in CA cells, but DCA sensitized doxorubicin-induced AA cell death. Expression of heat shock proteins (HSPs) were inhibited only in AA cells upon doxorubicin alone or combined treatment of DCA with doxorubicin, whereas Taxol alone or in combination with DCA did not show any changes in the levels of HSPs. DCA suppressed the metastatic features and reduced the population of cancer stem cell-like cells in CA cells but had a little effect on AA cells. Therefore, anticancer agents that can effectively restore mitochondria function may provide new therapeutic potential in reducing PCa health disparity and poor prognosis in AA men with PCa. Citation Format: Ajay K. Chaudhary, Tariq A. Bhatt, Sandeep Kumar, Willie Underwood, Shahriar Koochekpour, Mojgan Shourideh, Neelu Yadav, Dhyan Chandra. Mitochondria dysfunction-mediated apoptosis resistance associates with defective heat shock protein response in African American prostate cancer. [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 2936. doi:10.1158/1538-7445.AM2015-2936
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