ATM and LKB1 dependent activation of AMPK sensitizes cancer cells to etoposide-induced apoptosis

The present study aims to determine the effect of AMPK on etoposide-induced apoptosis of cancer cells. Our results revealed that etoposide induced AMPK activation in prostate C4-2 cancer cells, an event that was attenuated by ATM siRNA. In A549 cells that lack LKB1, AMPK was unable to be activated by etoposide, which was restored by introduction of LKB1. Likewise, silencing LKB1 in C4-2 cells impaired AMPK activation. Finally, etoposide displayed a potent pro-apoptotic effect in cancer cells with functional LKB1 and AMPK. Thus, our results establish a linear relationship of ATM, LKB1 and AMPK in response to the DNA damage drug.

► The role of AMPK in anti-cancer effect of DNA damaging agent has not been clearly defined.
► The present study shows that etoposide activates AMPK in an ATM and LKB1 dependent manner.
► We also find that activation of AMPK by etoposide renders cancer cells more senstive to.apoptosis.
► Our data suggest that AMPK can serve as a neoadjuvantchemotherapeutic target.