The potential implications of estrogenic and antioxidant-dependent activities of high doses of methyl paraben on MCF7 breast cancer cells.

Abstract

Methyl paraben (MP) is an endocrine-disrupting compound that possesses estrogenic properties and contributes to an aberrant burden of estrogen signaling in the human breast and subsequently increasing the risks for the development of breast cancer. The exact exposure, as well as the safe concentrations, are variable among daily products. The present study addresses the effects of exposure to escalated concentrations of MP on the proliferation of MCF-7 breast cancer cells in addition to exploring its other mechanisms of action. The study involved exposure of cultured MCF-7 breast cancer cells to seven MP concentrations, ranging from 40 to 800 µM for 5 days. Cell viability, apoptosis, and proliferation were respectively assessed using crystal violet test, flow cytometric analysis, and quantitative real-time polymerase chain reaction for Ki-67 expression. The estradiol (E2) secretion and oxidative stress were also assessed and analyzed in correlation to MP's proliferation and cytotoxicity potentials. The results showed that the maximum proliferative concentration of MP was 800 µM. At a concentration of 40 μM and higher, MP induced increased expression of Ki-67, denoting enhanced proliferation of the cells in monolayer culture. A positive correlation between the detrimental oxidative stress effect of MP's tested concentrations, cell proliferation, and viability was demonstrated (p < 0.05). Our results indicated that MP at high doses induced sustained cell proliferation due to E2 secretion as well as its antioxidant activity. Accordingly, it was concluded that high and unpredicted exposure to MP might carry a carcinogenic hazard on estrogen receptor-positive breast cancer cells.