α-pinene regulates miR-221 and induces G 2/M phase cell cycle arrest in human hepatocellular carcinoma cells

Biosci Rep. 2018 Dec 11;38(6):BSR20180980. doi: 10.1042/BSR20180980. Print 2018 Dec 21.

Abstract

The naturally occurring compound α-pinene induces cell cycle arrest and antitumor activity. We examined effects of α-pinene on cell cycle regulation in hepatocellular carcinoma cells (HepG2) cells to establish a foundation for its development as a novel treatment for hepatocellular carcinoma (HCC). HepG2 cells treated with α-pinene exhibited dose-dependent growth inhibition as a result of G2/M-phase cell cycle arrest. Cell cycle arrest was associated with down-regulated cyclin-dependent kinase 1 (CDK1) and miR-221 levels and up-regulated levels of CDKN1B/p27, γ-H2AX, phosphorylated ATM, phosphorylated Chk2 and phosphorylated p53. Our observations are consistent with a model in which α-pinene inhibits miR221 expression, which leads to G2/M-phase arrest and activation of CDKN1B/p27-CDK1 and ATM-p53-Chk2 pathways that suppress human hepatoma tumor progression. Additionally, α-pinene was found to trigger oxidative stress and induce apoptosis of HepG2 cells. α-pinene, therefore, represents a potential chemotherapeutic compound for the treatment of HCC.

Keywords: anti-hepatoma carcinoma; apoptosis; in vitro; miR-221; miRNA; α-pinene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Bicyclic Monoterpenes
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism
  • Down-Regulation / drug effects
  • G2 Phase Cell Cycle Checkpoints / drug effects*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism
  • M Phase Cell Cycle Checkpoints / drug effects*
  • MicroRNAs / genetics*
  • Monoterpenes / pharmacology*

Substances

  • Antineoplastic Agents
  • Bicyclic Monoterpenes
  • MIRN221 microRNA, human
  • MicroRNAs
  • Monoterpenes
  • alpha-pinene