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

Abstract

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.

Auranofin sensitizes breast cancer cells to paclitaxel mediated cell death via regulating FOXO3/Nrf2/Keap1 signaling pathway

“…It has been reported that auranofin displays anticancer activity against cancer cells through FOXO3 activation and the prevention of Nrf2 translocation to the nucleus 18 . Recently, we showed that auranofin treatment induces oxidative stress in the breast cancer cells which contributes for paclitaxel mediated apoptotic cell death 19 . In this present study, we elucidated the role of FOXO3/Nrf2/Keap1 signaling in the auranofin and paclitaxel mediated apoptotic cell death in the breast cancer cells.…”

“…18 Recently, we showed that auranofin treatment induces oxidative stress in the breast cancer cells which contributes for paclitaxel mediated apoptotic cell death. 19 In this present study, we elucidated the role of FOXO3/Nrf2/Keap1 signaling in the auranofin and paclitaxel mediated apoptotic cell death in the breast cancer cells.…”