MEHP-induced oxidative DNA damage and apoptosis in HepG2 cells correlates with p53-mediated mitochondria-dependent signaling pathway

Food Chem Toxicol. 2012 Jul;50(7):2424-31. doi: 10.1016/j.fct.2012.04.023. Epub 2012 Apr 21.

Abstract

In the present study, the effects of MEHP on human hepatocellular liver carcinoma HepG2 cells were investigated. The results showed that MEHP-induced oxidative DNA damage in the treatment groups (≥ 25.00 μM) at 24h after treatment and in the 100.00 μM treatment group at 36 h after treatment (p < 0.05 or p < 0.01). At 36 h after treatment, MEHP at higher concentrations (≥ 25.00 μM) resulted in a decrease in ATP level, and an increase in the protein levels of cytochrome c and Smac/DIABLO in the cytosol as well as the percentage of apoptotic cells. The activation of caspase-9 and -3 and the expression of the selected apoptosis-related proteins, p53, PUMA, NOXA, Bax and Bcl-2 were also induced. Furthermore, vitamin C, a scavenger of reactive oxygen species, attenuated MEHP-induced apoptosis. These findings indicated that MEHP induced oxidative DNA damage and apoptosis in HepG2 cells, and p53 and its downstream proteins were involved in mitochondria- and caspase-mediated apoptosis induced by MEHP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Caspase 3 / metabolism
  • Caspase 9 / metabolism
  • Cell Line, Tumor
  • DNA Damage / drug effects*
  • Diethylhexyl Phthalate / analogs & derivatives*
  • Diethylhexyl Phthalate / toxicity
  • Flow Cytometry
  • Humans
  • In Situ Nick-End Labeling
  • Mitochondria / metabolism*
  • Oxidative Stress / drug effects*
  • Signal Transduction*
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Tumor Suppressor Protein p53
  • Diethylhexyl Phthalate
  • Caspase 3
  • Caspase 9
  • mono-(2-ethylhexyl)phthalate