A novel chenodeoxycholic acid-verticinone ester induces apoptosis and cell cycle arrest in HepG2 cells

Steroids. 2012 Nov;77(13):1381-90. doi: 10.1016/j.steroids.2012.08.013. Epub 2012 Sep 4.

Abstract

In this study, the in vitro antitumor activity of chenodeoxycholic acid-verticinone ester (CDCA-Ver), a novel compound and its underlying mechanisms were evaluated. Results showed that CDCA-Ver significantly inhibited HepG2 cell viability in a both dose- and time-dependent manner, moreover CDCA-Ver induced apoptotic cell death and G(0)/G(1) cell cycle arrest in HepG2 cells. ROS generation, loss of balance of Bax/Bcl-2 ratio, loss of mitochondrial transmembrane potential, activation of caspases and elevation of intracellular free Ca(2+) concentration were involved in the CDCA-Ver induced apoptosis pathway in HepG2 cells. We concluded that CDCA-Ver may be a potential candidate for the therapy of cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects*
  • Calcium / metabolism
  • Caspases / metabolism
  • Cell Proliferation / drug effects
  • Cevanes / chemistry*
  • Cevanes / pharmacology*
  • Chenodeoxycholic Acid / chemistry*
  • Enzyme Activation / drug effects
  • Esters
  • G1 Phase Cell Cycle Checkpoints / drug effects*
  • Hep G2 Cells
  • Humans
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Reactive Oxygen Species / metabolism
  • Resting Phase, Cell Cycle / drug effects*
  • bcl-2-Associated X Protein / metabolism

Substances

  • Antineoplastic Agents
  • Cevanes
  • Esters
  • Proto-Oncogene Proteins c-bcl-2
  • Reactive Oxygen Species
  • bcl-2-Associated X Protein
  • Chenodeoxycholic Acid
  • verticine
  • Caspases
  • Calcium