Reactive oxygen species signaling in cancer: comparison with aging

Abstract

This work considers reactive oxygen species (ROS) signaling in solid tumors. Most (probably all) cancer cells are characterized by ROS overproduction that is they exist under conditions of incessant oxidative stress. For example ROS overproduction has been shown in prostate, pancreatic, melanoma, and glioma cells. ROS overproduction has been also demonstrated in breast, liver, bladder, colon, and ovarian cancers. Although these examples probably do not incorporate all the described data concerning ROS overproduction in cancer cells, they clearly support a proposal about enhanced oxidative stress in these cells. Therefore the mechanisms of ROS signaling in the survival and death of cancer cells and comparison with ROS signaling in senescent cells ought to be considered. It might be suggested that ROS overproduction in cancer cells is a major origin of their survival and resistance to anticancer treatment while the enhanced oxidative stress responsible for aging development. However it is of particular interest that additional ROS production by prooxidants can induce apoptosis in cancer cells. We suggest that moderate oxidative stress can stimulate proliferation and survival of cancer sells by conditioning mechanism while the enhancement of ROS overproduction by prooxidants under severe oxidative stress results in apoptosis and cell death. Aging development is always characterized by harmful ROS overproduction although the moderate increase in ROS formation in senescent cells might be not dangerous. Similar double-edged sword effects of ROS might be observed during the development of other pathologies for example diabetes mellitus.

Keywords: ROS; aging; cancer; signaling.

Figure 1.

ROS signaling in processes catalyzed by protein kinase B (Akt) leading to survival or apoptosis of cancer cells.

Figure 2.

ROS signaling in processes catalyzed by protein kinase JNK leading to apoptosis, cell cycle arrest, or proliferation of cancer cells.

Figure 3.

ROS signaling in survival, apoptosis, and proliferation processes catalyzed by JAK2 p38, ERK1/2, and p66Shc in cancer cells.

Figure 4.

Major ROS survival/death signaling pathways in cancer cells.