Germacrone inhibits the proliferation of breast cancer cell lines by inducing cell cycle arrest and promoting apoptosis

Eur J Pharmacol. 2011 Sep 30;667(1-3):50-5. doi: 10.1016/j.ejphar.2011.03.041. Epub 2011 Apr 9.

Abstract

Traditional medicinal herbs are an untapped source of potential pharmaceutical compounds. This study aims to determine whether the proliferation of breast cancer cell lines could be inhibited by germacrone, a natural product isolated from Rhizoma curcuma. Germacrone treatment significantly inhibited cell proliferation, increased lactate dehydrogenase (LDH) release, and induced mitochondrial membrane potential (ΔΨm) depolarization in both MCF-7 and MDA-MB-231 cells in a dose-dependent manner. Germacrone induced MDA-MB-231 and MCF-7 cell cycle arrest at the G0/G1 and G2/M phases respectively and induced MDA-MB-231 cell apoptosis. Furthermore, germacrone treatment significantly increased Bok expression and cytochrome c release from mitochondria without affecting Bcl-2, Bcl-xL, Bax, and Bim protein expressions. In addition, germacrone treatment induced caspase-3, 7, 9, PARP cleavage. We concluded that germacrone inhibited the proliferation of breast cancer cell lines by inducing cell cycle arrest and apoptosis through mitochondria-mediated caspase pathway. These results might provide some molecular basis for the anti-tumor activity of Rhizoma curcuma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Breast Neoplasms / pathology*
  • Caspases / metabolism
  • Cell Cycle Checkpoints / drug effects*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cytochromes c / metabolism
  • Drugs, Chinese Herbal / pharmacology*
  • Female
  • Humans
  • L-Lactate Dehydrogenase / metabolism
  • Membrane Potential, Mitochondrial / drug effects
  • Sesquiterpenes, Germacrane / pharmacology*
  • Signal Transduction / drug effects

Substances

  • Antineoplastic Agents
  • Drugs, Chinese Herbal
  • Sesquiterpenes, Germacrane
  • germacrone
  • Cytochromes c
  • L-Lactate Dehydrogenase
  • Caspases