Natarajan Deepika, Prasad N Rajendra, Sudharsan M, Bharathiraja Pradhapsingh, Lakra Deepa Swati
Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar, Tamil Nadu, India.
Cell Biochem Funct. 2023 Dec;41(8):1305-1318. doi: 10.1002/cbf.3865. Epub 2023 Oct 4.
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.
癌细胞的内在氧化还原状态限制了化疗药物的疗效。金诺芬是一种经美国食品药品监督管理局批准的含金化合物，在人体中具有有效的药代动力学和安全性，最近被重新用于抗癌活性研究。本研究通过靶向MDA-MB-231和MCF-7乳腺癌细胞系中的氧化还原平衡，研究了金诺芬对紫杉醇的增敏作用。金诺芬处理会消耗超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶的活性，并改变乳腺癌细胞系中的氧化还原比率。此外，还发现金诺芬在MDA-MB-231和MCF-7细胞系中均以浓度依赖性方式增强了紫杉醇介导的细胞毒性。此外，金诺芬以浓度依赖性方式增加了细胞内活性氧水平（使用2,7-二乙酰二氯荧光素二乙酸酯染色观察），并随后改变了线粒体膜电位（罗丹明-123染色）。此外，与单独使用紫杉醇治疗相比，在金诺芬加紫杉醇治疗的乳腺癌细胞中发现凋亡标志物p21的表达更高。因此，本研究结果表明金诺芬通过氧化代谢在MDA-MB-231和MCF-7乳腺癌细胞系中具有化学增敏特性。因此，在癌症化疗期间，金诺芬可被视为一种化学增敏剂。
