Augmentation of oxidative stress-induced apoptosis in MCF7 cells by ascorbate-tamoxifen and/or ascorbate-juglone treatments

作者：Sajadimajd Soraya; Yazdanparast Razieh^*; Roshanzamir Fariba

来源：In Vitro Cellular & Developmental Biology-Animal, 2016, 52(2): 193-203.

DOI：10.1007/s11626-015-9961-4

• Ascorbate
• Chemosensitization
• Juglone
• MCF7 cells
• Oxidative stress
• Tamoxifen

Since reactive oxygen species (ROS) play diverse roles in cancer, modulating the redox status of cancerous cells seems to be a promising therapeutic approach. Oxidant-targeted therapy appears logical for intervention with the acquired adaptive response to oxidative stress in cancer. In this study, we investigated the cytotoxic effects of juglone (J) and tamoxifen (T) and also the combination of each with ascorbate (A): tamoxifen/ascorbate (TA) and/or juglone/ascorbate (JA) on MCF7 cancerous cells. The results revealed that the growth inhibitory effects of juglone and tamoxifen were each associated with enhanced levels of ROS production and lipid peroxidation. These effects were markedly intensified in tamoxifen/ascorbate and juglone/ascorbate co-treatments. On the other hand, the intracellular anti-oxidant components such as reduced glutathione (GSH), catalase, superoxide dismutase (SOD), and glutathione peroxidase significantly declined in cells subjected to combination treatments compared to that in cells exposed solely to tamoxifen, juglone, and the untreated control cells. In addition, ascorbate association induced more apoptotic and necrotic or necrotic-like cell death than cells treated with each drug alone. These results were further confirmed by comparing the Bax/Bcl2 ratio in combination-treated cells. Additionally, ascorbate was able to potentiate the cytotoxic effects of combination therapy via activation of ROS-responsive factors including Foxo family members.

• 出版日期2016-2