A matter of balance between life and death: targeting reactive oxygen species (ROS)-induced autophagy for cancer therapy.
Reactive oxygen species (ROS) have been implicated in many biological functions and diseases. Often their role is counterintuitive, where ROS can either promote cell survival or cell death depending on the cellular context. Similarly, autophagy is involved in many biological functions and diseases where it can either promote cell survival or cell death. There is now a growing consensus that ROS controls autophagy in multiple contexts and cell types. Furthermore, alterations in ROS and autophagy regulation contribute to cancer initiation and progression. However, how ROS and autophagy contribute to cancer and how to target either for cancer treatment is controversial. Blocking ROS generation could prevent cancer initiation, whereas blockage of autophagy seems to be required for initiation of cancer. In cancer progression, high levels of ROS correspond with increased metabolism and under metabolic stress autophagy is required to maintain cellular integrity. In cancer treatment, therapeutic drugs that increase ROS and autophagy have been implicated in their mechanism for cell death, such as 2-methoxyestrodial (2-ME) and arsenic trioxide (As(2)O(3)), whereas other therapeutic drugs that induce ROS and autophagy seem to have a protective effect. This has led to different approaches to treat cancer patients where autophagy is either activated or inhibited. Both views of ROS and autophagy are valid and reflect the balance within a cell to either survive or die. Understanding this balancing act within a cell is essential to determine whether to block or activate ROS-controlled autophagy for cancer therapy.
Gibson
Spencer B
SB
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000627:therapeutic use; D001343:Autophagy / Q000502:physiology*; D045744:Cell Line, Tumor; D006801:Humans; D008623:Mercaptoethanol / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy*; D018384:Oxidative Stress / Q000502:physiology; D010087:Oxides / Q000627:therapeutic use; D017382:Reactive Oxygen Species / Q000378:metabolism*
D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D017382:Reactive Oxygen Species; D008623:Mercaptoethanol; D000077237:Arsenic Trioxide