Palbociclib induces activation of AMPK and inhibits hepatocellular carcinoma in a CDK4/6-independent manner.

ABSTRACT: Palbociclib, a CDK4/6 inhibitor, has recently been approved for hormone receptor-positive breast cancer patients. The effects of palbociclib as a treatment for other malignancies, including hepatocellular carcinoma (HCC), are of great clinical interest and are under active investigation. Here, we report the effects and a novel mechanism of action of palbociclib in HCC. We found that palbociclib induced both autophagy and apoptosis in HCC cells through a mechanism involving 5' AMP-activated protein kinase (AMPK) activation and protein phosphatase 5 (PP5) inhibition. Blockade of AMPK signals or ectopic expression of PP5 counteracted the effect of palbociclib, confirming the involvement of the PP5/AMPK axis in palbociclib-mediated HCC cell death. However, CDK4/6 inhibition by lentivirus-media

SUBMITTER: Hsieh FS 

PROVIDER: S-EPMC5537702 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature