The Janus-Faced Role of Antioxidants in Cancer Cachexia: New Insights on the Established Concepts

Figure 4

Hypothetical model for the eventual beneficial or deleterious interactions of antioxidants with tumor. ROS play a Janus-faced role by controlling both tumor growth and arrest. The levels of ROS produced within tumor depend on tumor type/localization and whether or not patient is undergoing radio/chemotherapy. Moderate-to-high ROS levels promote tumor proliferation, resulting in an increase in the levels of tumor-derived factors and the subsequent development of muscle atrophy. While high-to-excessive production of ROS activates tumor apoptosis and reduces the related catabolic response, the supplementation with antioxidants may decrease ROS at both systemic and muscular level but could also interact with tumor leading sometimes to undesirable consequences. For example, when excessive levels of ROS are produced within tumor, megadoses of antioxidants, used randomly, could increase tumor proliferation and/or inhibit apoptosis, by reducing oxidative damage in tumor cells. On the other hand, an appropriate use of antioxidants can decrease the risk of cancer development or even slow ROS-dependent cancer growth. The probability of reaping these antioxidant-related benefits could be much higher when supplementation is provided on a single-patient basis.