Phthalates are mainly used as substances added to plastics for increase flexibility, durability and transparency. Although phthalates have been reported to act as endocrine-disrupting chemicals (EDCs) and appear to cause detrimental effects on human health, diverse cancers and diseases, exact effect(s) and underlying mechanism(s) remain uncovered. The estrogenic activity of EDCs is partially associated with ability to stimulate cell viability in estrogen-dependent cancers expressing estrogen receptors (ERs), i.e. breast and ovarian cancers. 17β-estradiol (E2) as endogenous estrogens is an important factor in tumor growth and progression of estrogen-dependent diseases. In this study, we examined the effects of diverse phthalates, i.e. benzylbutyl phthalate (BBP) and diisobutyl phthalate (DiBP), on the expressions of cell cycle genes, i.e. p21, cyclin D1, and ER-α by RT-PCR analysis. In addition, the cell viability effect of phthalates was examined in BG-1 human ovarian cancer cells by MTT assay. To evaluate the ability of phthalates on cell proliferation, BG-1 cells were cultured in media added with negative control (0.1% DMSO), positive control (E2 1×10−9 M), BBP and DiBP (1×10−5 to 1×10−8 M). As a positive control, E2 markedly increased BG-1 cell proliferation compared to DMSO. Also BBP increased BG-1 cell proliferation at 1×10−5 and 1×10−6 M dose. In addition, DiBP increased BG-1 cell proliferation at 1×10−5 M dose. These results demonstrated that phthalates promotes the proliferation of BG-1 human ovarian cancer cells similar to E2. In addition, the expression levels of cell cycle related genes, p21, cyclin D1, and ER-α, were determined by RT-PCR. E2, BBP and DiBP decreased the expression levels of p21 and ER-α mRNAs in a time-dependent manner (0, 6 and 24 h), while the expression level of cyclin D1 mRNA increased. In this study, protein levels of p21, cyclin D1 and ER-α are being examined at the moment, and in vivo animal study is being studied to examine disruptive effects of phthalates on endocrine and reproductive systems.
Keywords: Phthalates, endocrine-disrupting chemicals, ovarian cancer, cell cycle gene, estrogen receptor-α.
03 - 07 May 2014
European Society of Endocrinology