Cooperation of bisphenol A and leptin in inhibition of caspase-3 expression and activity in OVCAR-3 ovarian cancer cells

Toxicol In Vitro. 2013 Sep;27(6):1937-43. doi: 10.1016/j.tiv.2013.06.017. Epub 2013 Jul 9.

Abstract

This study was designed to investigate the effect of bisphenol A and leptin on caspase-3 expression and activity in OVCAR-3 ovarian cancer cells. Caspase-3 and survivin expression was measured at the transcript level by real-time PCR and at the protein level by Western blotting. In addition, caspase-3 activity was measured, using a fluorometric assay, upon exposure to bisphenol A (40 nM) alone, leptin (2.5 nM) alone, and the combination of both agents. 17β-estradiol (40 nM) was used as a positive control for estrogenic properties of bisphenol A. Results showed that the interaction between bisphenol A and leptin, which was similar to that observed between 17β-estradiol and leptin, led to the inhibition of caspase-3 expression and activity in OVCAR-3 cells. Surprisingly, survivin was found to not be involved in the anti-apoptotic activity of either agent. Also, results showed that leptin inhibits caspase-3 activity by acting on the signal transducers and activators of transcription 3 (STAT3) pathway, but bisphenol A and 17β-estradiol by the extracellular-signal-regulated kinases 1/2 (ERK1/2) pathway. In conclusion, the study reveals that bisphenol A and leptin interact to inhibit caspase-3 expression and activity by modulating STAT3 and ERK1/2 signaling pathways in OVCAR-3 cells.

Keywords: Bisphenol A; Caspase-3; ERK1/2; Leptin; OVCAR-3; STAT3; Survivin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzhydryl Compounds / administration & dosage*
  • Caspase 3 / genetics
  • Caspase 3 / metabolism*
  • Caspase Inhibitors / administration & dosage*
  • Cell Line, Tumor
  • Estradiol / administration & dosage
  • Estrogens / administration & dosage
  • Estrogens, Non-Steroidal / administration & dosage*
  • Female
  • Humans
  • Inhibitor of Apoptosis Proteins / genetics
  • Inhibitor of Apoptosis Proteins / metabolism
  • Janus Kinases / antagonists & inhibitors
  • Janus Kinases / metabolism
  • Leptin / administration & dosage*
  • MAP Kinase Signaling System / drug effects
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / metabolism
  • Ovarian Neoplasms / metabolism*
  • Phenols / administration & dosage*
  • Phosphatidylinositol 3-Kinases
  • Protein Kinase Inhibitors / pharmacology
  • Proto-Oncogene Proteins c-akt
  • STAT3 Transcription Factor / antagonists & inhibitors
  • STAT3 Transcription Factor / metabolism
  • Survivin

Substances

  • BIRC5 protein, human
  • Benzhydryl Compounds
  • Caspase Inhibitors
  • Estrogens
  • Estrogens, Non-Steroidal
  • Inhibitor of Apoptosis Proteins
  • Leptin
  • Phenols
  • Protein Kinase Inhibitors
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Survivin
  • Estradiol
  • Phosphatidylinositol 3-Kinases
  • Janus Kinases
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinases
  • Caspase 3
  • bisphenol A