Abstract 5311: Auranofin sensitizes paclitaxel induced apoptotic cell death through oxidative mechanism in breast cancer cells

Abstract

Abstract Breast cancer cells exhibit several basal redox systems, thus poorly responding to oxidative cell death. These intrinsic redox statuses capitalize on the efficacy of chemotherapeutic drugs. Auranofin, an FDA-approved gold compound documented with effective pharmacokinetics and safety profiles in humans, has recently been repurposed for anticancer activity. This study examined the paclitaxel sensitizing effect of auranofin by targeting redox balance in the MDA-MB-231 and MCF-7 breast cancer cell lines. We observed that auranofin inhibits thioredoxin reductase activity (TrxR) in these breast cancer cells and collapses the cellular antioxidants status, including the reduced activities of superoxide dismutase, catalase, and glutathione peroxidase. Furthermore, it has been noticed that auranofin augmented paclitaxel mediated cytotoxicity in a concentration dependant manner in both the MDA-MB-231 and MCF-7 cell lines. Furthermore, auranofin increased intracellular ROS levels (DCFH-DA staining) and altered mitochondrial membrane potential (Rhodamine-123 staining) in these breast cancer cell lines. The proapoptotic markers such as p53, Bax, and caspase-3 and caspase-9 expressions were higher in auranofin plus paclitaxel treated breast cancer cells when compared to paclitaxel alone treatment. Thus, the present results illustrate the chemosensitizing property of auranofin in MDA-MB-231 and MCF-7 breast cancer cell lines. Citation Format: N. Rajendra Prasad, Deepika Natarajan. Auranofin sensitizes paclitaxel induced apoptotic cell death through oxidative mechanism in breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5311.