Activation of c-Met in cancer cells mediates growth-promoting signals against oxidative stress through Nrf2-HO-1.

ABSTRACT: Any imbalance between reactive oxygen species (ROS) generation and the anti-oxidant capacity lead to cellular oxidative stress. Many chemotherapeutic agents mediate their cytotoxic functions through the generation of ROS. c-Met, a receptor tyrosine kinase, is over-expressed in renal cancer and plays very crucial role(s) in its growth and survival. Here, we show that c-Met activation protected renal cancer cells from ROS, oxidative stress and cytotoxicity induced by the anti-cancer agent sorafenib (used for renal cancer treatment); and it markedly attenuated sorafenib-induced DNA damage. Activated c-Met promoted the anti-apoptotic proteins (Bcl-2 and Bcl-xL) and inhibited apoptotic cleaved caspase-3. We found that the cytoprotective function of c-Met against sorafenib-induced ROS generation

SUBMITTER: Chakraborty S 

PROVIDER: S-EPMC6333845 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature