Auranofin sensitizes breast cancer cells to paclitaxel chemotherapy by disturbing the cellular redox system

• Published in: Cell biochemistry and function Vol. 41; no. 8; pp. 1305 - 1318
• Main Authors: Natarajan, Deepika, Prasad, N. Rajendra, Sudharsan, M., Bharathiraja, Pradhapsingh, Lakra, Deepa Swati
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.12.2023
• Subjects: Anticancer properties; antioxidants; Antitumor activity; Apoptosis; auranofin; Breast cancer; Catalase; Cell cycle; Cell death; chemosensitization; Chemotherapy; Cytotoxicity; Diacetyl; FDA approval; Glutathione; Glutathione peroxidase; Intracellular; Membrane potential; Metabolism; Oxidative metabolism; Paclitaxel; Peroxidase; Pharmacokinetics; Reactive oxygen species; redox status; Rhodamine; Sensitizing; Staining; Superoxide dismutase; Toxicity; Tumor cell lines; auranofin; breast cancer; chemosensitization; redox status; antioxidants
• ISSN: 0263-6484; 1099-0844
• DOI: 10.1002/cbf.3865

The intrinsic redox status of cancer cells limits the efficacy of chemotherapeutic drugs. Auranofin, a Food and Drug Administration‐approved gold‐containing 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. Auranofin treatment depletes the activities of superoxide dismutase, catalase, and glutathione peroxidase and alters the redox ratio in the breast cancer cell lines. Furthermore, it has been noticed that auranofin augmented paclitaxel‐mediated cytotoxicity in a concentration‐dependent manner in both MDA‐MB‐231 and MCF‐7 cell lines. Moreover, auranofin increased the levels of intracellular reactive oxygen species (observed using 2, 7‐diacetyl dichlorofluorescein diacetate staining) and subsequently altered the mitochondrial membrane potential (rhodamine‐123 staining) in a concentration‐dependent manner. Further, the expression of apoptotic marker p21 was found to be higher in auranofin plus paclitaxel‐treated breast cancer cells 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 via oxidative metabolism. Therefore, auranofin could be considered a chemosensitizing agent during cancer chemotherapy. Significance statement In this study, auranofin, a Food and Drug Administration‐approved drug, has been repurposed for anticancer activity. The results illustrate that auranofin improved paclitaxel‐mediated cytotoxicity in breast cancer cell lines. The auranofin treatment altered the intracellular redox balance in the breast cancer cells, which contributes to paclitaxel‐mediated cell cycle arrest and subsequent apoptotic cell death. Thus, the present results illustrate the chemosensitizing property of auranofin in breast cancer cell lines via oxidative metabolism. Therefore, auranofin could be considered a chemosensitizing agent during cancer chemotherapy.