Eupalinolide J induces apoptosis, cell cycle arrest, mitochondrial membrane potential disruption and DNA damage in human prostate cancer cells

J Toxicol Sci. 2020;45(1):15-23. doi: 10.2131/jts.45.15.

Abstract

Eupalinolide J (EJ) is a new sesquiterpene lactone isolated from Eupatorium lindleyanum DC. In the present study, we investigated the anti-cancer activity of EJ on cell proliferation in human prostate cancer cells. The MTT results indicated that EJ showed marked anti-proliferative activity in PC-3 and DU-145 cells in a dose- and time-dependent manner. DAPI staining analysis demonstrated that this effect was mediated by induction of cell apoptosis. Flow cytometric analysis indicated a significant increase in apoptotic cells, cell cycle arrest at G0/G1 phase and disruption of mitochondrial membrane potential (MMP) after EJ treatment. Meanwhile, the activation of caspase-3 and caspase-9 was visibly observed. Furthermore, our results demonstrated that the expression levels of γH2AX, p-Chk1 and p-Chk2 were significantly up-regulated, suggesting the induction of DNA damage responses in EJ-treated prostate cancer cells. The above results indicated that EJ exhibited effective anti-cancer activity in vitro. It could be a promising candidate agent for the clinical treatment of prostate cancer.

Keywords: Apoptosis; Cell cycle; DNA damage response; Eupalinolide J; Prostate cancer.

MeSH terms

  • Apoptosis / drug effects*
  • Cell Cycle Checkpoints / drug effects*
  • Eupatorium / chemistry
  • Humans
  • Male
  • Membrane Potentials / drug effects*
  • Mitochondria / drug effects*
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology*
  • Tumor Cells, Cultured