Differential sensitivities of triple-negative breast cancer stem cell towards various doses of vitamin C: An insight into the internal antioxidant systems.

Cancer stem cells (CSCs) are quiescent and self-renewing, having low levels of reactive oxygen species (ROS), and are responsible for cancer recurrence after chemotherapy and radiotherapy. However, the interplay between the ROS production and scavenging from the oxidative stress has never been studied in breast CSCs. In this present study, we have investigated the cellular energetics of two triple-negative breast cancer stem cells (MDA-MB-231 and MDA-MB-468) treated with two pharmacological doses of vitamin C (10 and 20 mM) that generated ROS. Our results indicate a differential behavior of ROS scavenging by both the CSCs. MDA-MB-468 CSCs exhibited higher resistance to ROS induced damage owing to the higher antioxidant activity, lower mitochondrial damage, and less decrease in membrane potential (ΔΨ ) as compared with MDA-MB-231 CSCs. Moreover, MDA-MB-231 CSCs exhibited an intrinsic apoptosis pathway by activating the cytochrome c, caspase-9, 3, 7, and cleaved PARP upon treatment with vitamin C. This data suggests a possible strategy for targeting breast CSCs using vitamin C. Taken together, the CSCs from MDA-MB-231 could be easily targeted by high/pharmacological doses of vitamin C (≥20 mM) thereby indicating a less robust internal antioxidant machinery.