title: Cooperation of bisphenol A and leptin in inhibition of caspase-3 expression and activity in OVCAR-3 ovarian cancer cells.
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.
authors.affiliation: Department of Physiology and Toxicology of Reproduction, Chair of Animal Physiology, Institute of Zoology, Jagiellonian University, Krakow, Poland. anna.ptak@uj.edu.pl
authors.forename: Anna
authors.initials: A
authors.lastname: Ptak
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Rak-Mardyła
authors.forename: Ewa L
authors.initials: EL
authors.lastname: Gregoraszczuk
mesh_terms: D001559:Benzhydryl Compounds / Q000008:administration & dosage*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism*; D061945:Caspase Inhibitors / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D004958:Estradiol / Q000008:administration & dosage; D004967:Estrogens / Q000008:administration & dosage; D004968:Estrogens, Non-Steroidal / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D053612:Janus Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D020738:Leptin / Q000008:administration & dosage*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000378:metabolism*; D010636:Phenols / Q000008:administration & dosage*; D019869:Phosphatidylinositol 3-Kinases; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D000077022:Survivin; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D053148:Caspase 3; D061945:Caspase Inhibitors; D004958:Estradiol; D004967:Estrogens; D004968:Estrogens, Non-Steroidal; D051034:Inhibitor of Apoptosis Proteins; D053612:Janus Kinases; D020738:Leptin; D020928:Mitogen-Activated Protein Kinases; D010636:Phenols; D019869:Phosphatidylinositol 3-Kinases; D047428:Protein Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D050796:STAT3 Transcription Factor; D000077022:Survivin; C107489:BIRC5 protein, human; C494086:STAT3 protein, human; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Bisphenol A; Caspase-3; ERK1/2; Leptin; OVCAR-3; STAT3; Survivin