CDK4/6 inhibitor protects against myocardial cells apoptosis by inhibiting RB phosphorylation in H9c2 cells

Biochem Biophys Res Commun. 2019 Feb 19;509(4):949-953. doi: 10.1016/j.bbrc.2019.01.015. Epub 2019 Jan 12.

Abstract

Cell cycle dysregulation is typical in human cancers, and CDK4/6 inhibitors targeting cell cycle have potential antiapoptosis effect. The aim of this work is to identify the regulatory effect of Palbociclib on apoptosis of H9c2 cells induced by high glucose (HG) and to elucidate the fundamental mechanisms. It was observed that Palbociclib decreased intracellular ROS production, augmented mitochondrial membrane potential and hindered apoptosis of H9c2 cells. Palbociclib increased the Bcl-2/Bax ratio, diminished the expressions of Bax and cleaved-caspase-3, and affected the RB phosphorylation and p53 expression. Altogether, the anti-apoptotic efficacy of Palbociclib could be attributed in part to the modulation of the mitochondria apoptotic pathway.

Keywords: Apoptosis; Cell cycle; High glucose; Palbociclib; ROS generation.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects*
  • Cell Line
  • Cyclin-Dependent Kinase 4 / antagonists & inhibitors
  • Cyclin-Dependent Kinase 6 / antagonists & inhibitors
  • Glucose / pharmacology
  • Humans
  • Membrane Potential, Mitochondrial / drug effects
  • Myocytes, Cardiac / pathology*
  • Phosphorylation / drug effects
  • Piperazines / pharmacology*
  • Protective Agents / pharmacology
  • Pyridines / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Retinoblastoma Protein / metabolism

Substances

  • Antineoplastic Agents
  • Piperazines
  • Protective Agents
  • Pyridines
  • Reactive Oxygen Species
  • Retinoblastoma Protein
  • CDK4 protein, human
  • CDK6 protein, human
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinase 6
  • palbociclib
  • Glucose