Anticancer effects of O-desmethylangolensin are mediated through cell cycle arrest at the G2/M phase and mitochondrial-dependent apoptosis in Hep3B human hepatocellular carcinoma cells

Int J Mol Med. 2013 Mar;31(3):726-30. doi: 10.3892/ijmm.2013.1230. Epub 2013 Jan 8.

Abstract

In the present study, in order to investigate the anticancer effects of O-desmethylangolensin (O-DMA) on human hepatocellular carcinoma Hep3B cells, we first examined the antiproliferative effect of O-DMA. When Hep3B cells were treated with O-DMA at various concentrations (5-200 µM) for 24, 48 or 72 h, cell proliferation decreased significantly in a dose- and time-dependent manner. Moreover, O-DMA exposure at the IC50 concentration for 72 h arrested cells at the G2/M phase, which was accompanied by a reduction in CDK1, and an increase in cyclin A and B. Under the same conditions, O-DMA significantly increased the number of sub-G1 phase cells. Additionally, an Annexin V assay revealed that exposure to O-DMA affected the rate of cell apoptosis. O-DMA caused the downregulation of Bcl-2 and upregulation of Bax, which led to cytochrome c release from the mitochondria and activation of caspase-3. Taken together, these data suggest that O-DMA exhibits anticancer activity by arresting the cell cycle at G2/M phase and causing mitochondrial-dependent apoptosis in Hep3B cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • CDC2 Protein Kinase / biosynthesis
  • Carcinoma, Hepatocellular / drug therapy*
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cyclin A / biosynthesis
  • Cyclin B / biosynthesis
  • Cytochromes c / metabolism
  • G2 Phase Cell Cycle Checkpoints / drug effects*
  • Humans
  • Isoflavones / pharmacology*
  • Liver Neoplasms / drug therapy*
  • Mitochondria / metabolism
  • Phytoestrogens / pharmacology
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis

Substances

  • Antineoplastic Agents
  • Cyclin A
  • Cyclin B
  • Isoflavones
  • Phytoestrogens
  • Proto-Oncogene Proteins c-bcl-2
  • Cytochromes c
  • CDC2 Protein Kinase
  • Caspase 3
  • O-desmethylangolensin