The estrogenic proliferative effects of two alkylphenols and a preliminary mechanism exploration in MCF‐7 breast cancer cells
Xiaoxia Wang, Nao Luo, Zhixiang Xu, Xianyao Zheng, Bin Huang, Xuejun Pan
Abstract
Abstract Bisphenol A (BPA) and 4‐cumylphenol (4‐CP), as estrogen‐like chemicals, are ubiquitous in the environment media and associated with the occurrence and development of hormone‐dependent tumors. However, the combinatorial effects of these two structurally similar alkylphenols are not well informed. In the present study, the classic breast cancer cell line MCF‐7 was used as in vitro model to estimate the estrogenic proliferative effects of BPA and 4‐CP. MTT assay, reactive oxygen species, cell apoptosis, cell cycle, and real‐time fluorescent quantitative Step One Plus Real‐time PCR System (Applied Biosystems, CA, USA) were applied to explore their proliferative mechanisms. MTT results showed that both BPA and 4‐CP ranging from 10 −9 to 10 −5 M stimulated cell proliferation in a nonmonotonic dose‐response manner. Along with the proliferative effects, cell cycle was progressed from G0/G1 to S and G2/M phase. Meanwhile, the expression levels of ERα, pS2, and Bcl‐2 mRNA were also upregulated. In contrast, 4‐CP and BPA at high dose (10 −4 M) obviously displayed antiproliferative effects in MCF‐7 cells via inducing cell apoptosis and blocking cell cycle in G0/G1 phase. As expected, the relative expression levels of ERα, pS2, and Bcl‐2 mRNA were decreased, whereas Bax mRNA was increased. Interestingly, the proliferative or antiproliferative effects of 4‐CP were higher than that of BPA. Moreover, coexposure of lower concentrations BPA and 4‐CP significantly induced cell proliferation in a synergistic manner. These findings indicated that the potential environmental risks of coexposure of BPA and 4‐CP were greater than either of them.