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_m) 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.

中文翻译：

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三阴性乳腺癌干细胞对不同剂量维生素 C 的不同敏感性：对内部抗氧化系统的洞察

癌症干细胞 (CSC) 是静止的和自我更新的，具有低水平的活性氧 (ROS)，并且是化疗和放疗后癌症复发的原因。然而，从未在乳腺 CSC 中研究过 ROS 产生和氧化应激清除之间的相互作用。在本研究中，我们研究了两种三阴性乳腺癌干细胞（MDA-MB-231 和 MDA-MB-468）的细胞能量学，它们用两种药理剂量的维生素 C（10 和 20 mM）处理，产生 ROS . 我们的结果表明两种 CSC 清除 ROS 的行为不同。由于更高的抗氧化活性、更低的线粒体损伤和更少的膜电位下降（ΔΨ _m) 与 MDA-MB-231 CSC 相比。此外，MDA-MB-231 CSCs 在维生素 C 治疗后通过激活细胞色素c、caspase-9、3、7 和切割的 PARP表现出内在的凋亡途径。该数据表明使用维生素 C 靶向乳腺 CSCs 的可能策略。总之，来自 MDA-MB-231 的 CSC 可以很容易地被高/药理学剂量的维生素 C（≥20 mM）靶向，从而表明内部抗氧化机制不太强大。