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

Figure 1

The central role of tumor in the development of oxidative stress at multiple organs during cachexia. Tumor is the main responsible factor for the development of OS at different organs and the consecutive disruption of their vital functions. Indeed, chemicals released by tumor in the systemic circulation can reach multiple destinations like heart, muscle, and liver. For example, TNF-α and IL-6 can induce anorexia, leading to inadequate synthesis of reducing compounds like NADPH in the liver. Additionally, IL-6, TNF-α, and myostatin (Mstn) upregulate the activity of ROS-producing enzymes within heart/skeletal muscles, leading to the activation of several catabolic pathways and muscle proteolysis. As a direct result, heart/skeletal muscles are atrophied, oxidative injuries accumulated, and antioxidant (AO) defense becomes inefficient, giving way to multiorgan failure and cancer cachexia evolution.