Proliferative and apoptotic effects of bisphenol A and its combination with estradiol in human breast carcinoma cells
T. Havranek, L. Macho & M. Fickova
Bisphenol A (BPA) is an endocrine disruptor (ED) used as plasticiser present in plastic products of daily use. The leakage of BPA monomer into food, drinks represents the ubiquitous exposure to the general population. BPA stimulatory effect on breast cancer cells growth in vitro and increased incidence of hormone dependent malignancies suspected BPA from carcinogenic effect.
The aim of this study was to investigate the effects of BPA alone and in the combination with estradiol (E2, 110-12M, COM) on cell proliferation, DNA synthesis and proteins of apoptosis. The time (24, 48, 72h) and dose (1×10−151×10−6 M) dependent effects were compared to E2 in breast carcinoma cells MCF7. Cells were maintained in RPMI 1640 medium containing 5% dextran-charcoal-treated FBS. MTT test was used in proliferation experiments, BrdU incorporation into newly synthesized DNA was analyzed. The expressions of proapoptotic Bax, p53 and antiapoptotic Bcl-2 proteins were determined by Western blot.
Higher BPA concentrations moderately (~130%), but significantly increased proliferation (vs COM) after 48h as the consequence of previous (24 h) huge (180220%) increase of de novo DNA synthesis (vs E2, COM). The mixture E2 (1012 M)+BPA induced 140160% increase of DNA synthesis (vs BPA, E2) after 48 h, followed by enhanced proliferation (~140%, vs BPA, E2) after 72 h thus exceeding effects of individual compounds. The mixture had neither additive, nor synergic effect.
E2 (48 h) reduced p53 (by 20%) while BPA displayed a slight stimulation; E2+BPA inhibited p53 as E2. Similar tendencies of changes were observed in Bax protein. No modifications in Bcl-2 was present except moderate increase by BPA (vs E2 and COM) after 48 h.
BPA and mixture BPA+E2 stimulate MCF7 cells proliferation after preceding elevated DNA synthesis and by protein modification(s) of apoptosis.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This work was supported, however funding details unavailable.