Abstract
Reactive oxygen species (ROS) and ROS-dependent (redox regulation) signaling pathways and transcriptional activities are thought to be critical in stem cell self-renewal and differentiation during growth and organogenesis. Aberrant ROS burst and dysregulation of those ROS-dependent cellular processes are strongly associated with human diseases including many cancers. ROS levels are elevated in cancer cells partially due to their higher metabolism rate. In the past 15 years, the concept of cancer stem cells (CSCs) has been gaining ground as the subpopulation of cancer cells with stem cell-like properties and characteristics have been identified in various cancers. CSCs possess low levels of ROS and are responsible for cancer recurrence after chemotherapy or radiotherapy. Unfortunately, how CSCs control ROS production and scavenging and how ROS-dependent signaling pathways contribute to CSCs function remain poorly understood. This review focuses on the role of redox balance, especially in ROS-dependent cellular processes in cancer stem cells (CSCs). We updated recent advances in our understanding of ROS generation and elimination in CSCs and their effects on CSC self-renewal and differentiation through modulating signaling pathways and transcriptional activities. The review concludes that targeting CSCs by manipulating ROS metabolism/dependent pathways may be an effective approach for improving cancer treatment.
Highlights
Reactive oxygen species (ROS), hydrogen peroxide (H2O2), and including hydroxyl rsaudpiecraolx(iOdeH(∙O),2a−r)e, highly chemically reactive species derived from molecular oxygen [1, 2]
Phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a major negative regulator of PI3K, is a tumor suppressor [42]
hypoxia-inducible factor-1α (HIF-1α) is not affected in CD133+ tumor stem-like cells grown at 7% oxygen level but HIF-2α is expressed at higher levels as compared with that at 20% oxygen level [83]
Summary
Reactive oxygen species (ROS), hydrogen peroxide (H2O2), and including hydroxyl rsaudpiecraolx(iOdeH(∙O),2a−r)e, highly chemically reactive species derived from molecular oxygen [1, 2]. It is important for cells to balance ROS generation and antioxidant systems, and redox regulation of cellular process is essential for growth and development. CSCs are thought to have the ability to self-renew and differentiate [1] and be responsible for cancer recurrence after chemotherapy or radiotherapy as those cells can survive treatment and quickly generate new tumors [18, 19]. These abilities of CSCs lead to a view that cancer therapy strategies should target the normal cancer cells, and the CSCs. Considering the importance of redox balance in cancer cells, conventional therapies (chemotherapy or radiotherapy) targeting redox balance can kill most of the cancer cells [14, 20, 21]. With special attention given to the cross talk between CSC-related pathways and redox regulation, we hope to generate substantial interest in further investigating the role of redox regulation in CSCs and the utility of targeting ROS-dependent/redox regulation of pathways
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