More than Just an Immunosuppressant: The Emerging Role of FTY720 as a Novel Inducer of ROS and Apoptosis

Figure 4

ROS paradox and the concept of prooxidant cancer therapy. In precancerous conditions, ROS levels are slightly elevated which facilitate characteristic carcinogenic and mutagenic processes, including DNA, protein, and lipid damages, and stimulate tumor cell proliferation. Persistent exposure to ROS induces redox adaptation, including activation of redox-sensitive transcription factors (e.g., NF-κB, Nrf2, and HIF-1) that increase the expression of ROS-scavenging enzymes. Malignant cells exhibit higher steady-state levels of ROS due to an adaptive increase of antioxidant capacity. The high ROS levels in cancer cells render them more susceptible/vulnerable to further oxidative stress induced by exogenous ROS-generating agents. When the levels of ROS elevate above the threshold that cancer cells can adapt, cells can no longer survive leading to cell death.