Intracellular reactive oxygen species determine cancer stem cell radiosensitivity related to predictive biomarker for radiotherapy
Cancer cells display a higher level of reactive oxygen species (ROS) mainly due to increased metabolic activities resulting in altered redox balance. Imbalance in redox arises when the generation of ROS exceeds antioxidants defense system. ROS are generated in cells from multiple pathways, but mitoc...
Wolters Kluwer Medknow Publications
|Journal of Radiation and Cancer Research
|Cancer cells display a higher level of reactive oxygen species (ROS) mainly due to increased metabolic activities resulting in altered redox balance. Imbalance in redox arises when the generation of ROS exceeds antioxidants defense system. ROS are generated in cells from multiple pathways, but mitochondria contribute significantly to cellular ROS pool by oxidative phosphorylation. Elevated levels of ROS are implicated in cell transformation, proliferation, and tumorigenesis. ROS-mediated signaling pathways activate pro-oncogenes which regulate cancer progression, angiogenesis, and survival. Normal cells maintain intracellular homeostasis by developing an array of enzymatic antioxidant systems such as catalase, superoxide dismutase, and glutathione peroxidase. Chemotherapy and radiotherapy exert their cytotoxic effects on tumor cells by the generation of excessive ROS. The failure of therapies is attributable to a small fraction of core cells in tumor mass called cancer stem cells (CSCs) which have self-renewal property and exhibit proliferation, differentiation, and resistance to treatments. Both normal and CSCs maintain low-ROS level ascribed to stemness. This review describes role and relevance of ROS in CSC with particular emphasis on developing predictive biomarker for outcome of cancer radiotherapy. It is pointed out that CSCs maintain lower ROS homeostasis and evade cell death by increased level of endogenous antioxidants capacity in cancer cells. Search for regulators of ROS and surface markers in CSC may render them sensitive to radiation offering new and effective strategy for cancer treatment.