Anna Wróbel1, Ewa Ł Gregoraszczuk. 1. Department of Physiology and Toxicology of Reproduction, Jagiellonian University, Gronostajowa 9, PL 30-387 Kraków, Poland. ania.wrobel@uj.edu.pl
Abstract
BACKGROUND: Here, we analyzed the dose- (0.2, 2, 20, 200 nM or 2 μM) and time- (48, 96, 144 and 196 h) dependent activity of a single or repeated exposure of methyl-, butyl- and propylparaben on the proliferation of MCF-7 human breast cancer cells and MCF-10A human breast epithelial cells. Additionally, the effect on estradiol secretion, gene and protein expression of aromatase (CYP19A1) was investigated. METHODS: Cell proliferation was determined by AlamarBlue assay, and estradiol secretion by ELISA kits. Gene and protein expression of CYP19A1 was measurement using real time PCR and western blot, respectively. RESULTS: Stimulatory effect of a single exposure of all doses of tested parabens and time dependent effect of repeated exposure to methylparaben, propylparaben and butylparaben, the same as that of 17β-estradiol, on proliferation of MCF-7 cells was observed. Only at low doses methyl- and butylparabens increased MCF-10A cells proliferation after single exposure, but no effect of repeated exposure was noted. Exposure at low doses of all of the parabens significantly increased 17β-estradiol (E2) secretion in MCF-7 cells but had the opposite effect on MCF-10A cells. It was correlated with gene and protein expression of CYP19A1 in MCF-7 and MCF-10 cells. CONCLUSIONS: In summary, present study indicates a different mechanism of proliferative action of parabens in investigated cell lines. In MCF-7 breast cancer cell line it is probably due to stimulatory action on estradiol secretion and aromatase activity. In MCF-10A by an unknown mechanism, independent on stimulatory action on estradiol section, which requires further investigation.
BACKGROUND: Here, we analyzed the dose- (0.2, 2, 20, 200 nM or 2 μM) and time- (48, 96, 144 and 196 h) dependent activity of a single or repeated exposure of methyl-, butyl- and propylparaben on the proliferation of MCF-7 humanbreast cancer cells and MCF-10A human breast epithelial cells. Additionally, the effect on estradiol secretion, gene and protein expression of aromatase (CYP19A1) was investigated. METHODS: Cell proliferation was determined by AlamarBlue assay, and estradiol secretion by ELISA kits. Gene and protein expression of CYP19A1 was measurement using real time PCR and western blot, respectively. RESULTS: Stimulatory effect of a single exposure of all doses of tested parabens and time dependent effect of repeated exposure to methylparaben, propylparaben and butylparaben, the same as that of 17β-estradiol, on proliferation of MCF-7 cells was observed. Only at low doses methyl- and butylparabens increased MCF-10A cells proliferation after single exposure, but no effect of repeated exposure was noted. Exposure at low doses of all of the parabens significantly increased 17β-estradiol (E2) secretion in MCF-7 cells but had the opposite effect on MCF-10A cells. It was correlated with gene and protein expression of CYP19A1 in MCF-7 and MCF-10 cells. CONCLUSIONS: In summary, present study indicates a different mechanism of proliferative action of parabens in investigated cell lines. In MCF-7 breast cancer cell line it is probably due to stimulatory action on estradiol secretion and aromatase activity. In MCF-10A by an unknown mechanism, independent on stimulatory action on estradiol section, which requires further investigation.
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