Manipal Institute of Regenerative Medicine, Manipal Academy of Higher Education (MAHE), Bangalore, Karnataka, India.
Division of Cancer Stem Cells and Cardiovascular Regeneration, Manipal Institute of Regenerative Medicine, Manipal Academy of Higher Education, Bangalore, Karnataka, India.
J Cell Biochem. 2024 Jan;125(1):3-21. doi: 10.1002/jcb.30506. Epub 2023 Nov 24.
Reactive oxygen species (ROS) and its related signaling pathways and regulating molecules play a major role in the growth and development of cancer stem cells. The concept of ROS and cancer stem cells (CSCs) has been gaining much attention since the past decade and the evidence show that these CSCs possess robust self-renewal and tumorigenic potential and are resistant to conventional chemo- and radiotherapy and believed to be responsible for tumor progression, metastasis, and recurrence. It seems reasonable to say that cancer can be cured only if the CSCs are eradicated. ROS are Janus-faced molecules that can regulate cellular physiology as well as induce cytotoxicity, depending on the magnitude, duration, and site of generation. Unlike normal cancer cells, CSCs expel ROS efficiently by upregulating ROS scavengers. This unique redox regulation in CSCs protects them from ROS-mediated cell death and nullifies the effect of radiation, leading to chemoresistance and radioresistance. However, how these CSCs control ROS production by scavenging free radicals and how they maintain low levels of ROS is a challenging to understand and these attributes make CSCs as prime therapeutic targets. Here, we summarize the mechanisms of redox regulation in CSCs, with a focus on therapy resistance, its various pathways and microRNAs regulation, and the potential therapeutic implications of manipulating the ROS levels to eradicate CSCs. A better understanding of these molecules, their interactions in the CSCs may help us to adopt proper control and treatment measures.
活性氧（ROS）及其相关信号通路和调节分子在癌症干细胞的生长和发育中起主要作用。自过去十年以来，ROS 和癌症干细胞（CSC）的概念受到了广泛关注，有证据表明这些 CSC 具有强大的自我更新和致瘤潜力，并且对常规化疗和放疗具有抗性，被认为是导致肿瘤进展、转移和复发的原因。如果能消灭 CSC，癌症似乎就能治愈，这似乎是合理的。ROS 是两面派分子，根据其产生的幅度、持续时间和部位，既能调节细胞生理，又能诱导细胞毒性。与正常癌细胞不同，CSC 通过上调 ROS 清除剂来有效排出 ROS。CSC 中这种独特的氧化还原调节保护它们免受 ROS 介导的细胞死亡，并使辐射失效，从而导致化疗耐药和放疗耐药。然而，CSC 如何通过清除自由基来控制 ROS 的产生，以及它们如何保持低水平的 ROS，这是一个难以理解的问题，这些特性使 CSC 成为主要的治疗靶点。在这里，我们总结了 CSC 中氧化还原调节的机制，重点介绍了治疗耐药性及其各种途径和 microRNAs 调节，以及操纵 ROS 水平以消灭 CSC 的潜在治疗意义。更好地了解这些分子及其在 CSC 中的相互作用，可能有助于我们采取适当的控制和治疗措施。
