Differential effect of methyl-, butyl- and propylparaben and 17[beta]-estradiol on selected cell cycle and apoptosis gene and protein expression in MCF-7 breast cancer cells and MCF-10A non-malignant cells

• Published in: Journal of applied toxicology Vol. 34; no. 9; p. 1041
• Main Authors: Wrobel, Anna Maria, Gregoraszczuk, Ewa ucja
• Format: Journal Article
• Language: English
• Published: Bognor Regis Wiley Subscription Services, Inc 01.09.2014
• Subjects: Apoptosis; Breast cancer; Cell cycle; Preservatives; Protein expression; Toxicology
• ISSN: 0260-437X; 1099-1263
• DOI: 10.1002/jat.2978

Parabens are alkyl esters of p-hydroxybenzoic acid used widely as antimicrobial preservatives in consumer products, including pharmaceuticals, foods and cosmetics. We showed previously that methyl-, butyl- and propylparaben parabens, even at low doses, stimulate the proliferation of MCF-7 breast cancer cells and non-transformed MCF-10A breast epithelial cells. The present study was undertaken to determine whether this represents a direct effect on cell cycle and apoptotic gene expression. MCF-7 and MCF-10A cells were exposed to methyl, butyl- and propylparaben (20nm) or 17[beta]-estradiol (10nm). Cell cycle and apoptotic gene expression were evaluated by real-time polymerase chain reaction and protein expression by Western blot. 17[beta]-estradiol upregulated G1/S phase genes and downregulated cell cycle progression inhibitors in both MCF-7 and MCF-10A. Upregulation of Bcl-xL and downregulation of caspase 9 was observed in MCF-7, while upregulation of Bcl-xL, BCL2L2 and caspase 9 was noted in MCF-10A. Cyclins in MCF-7 cells were not affected by any of the parabens. Methyl- and butylparaben had no effect on the expression of selected apoptotic genes in MCF-7. In MCF-10A, all parabens tested increased the expression of G1/S phase genes, and downregulated cell cycle inhibitors. Methylparaben increased pro-survival gene. Butylparaben increased BCL2L1 gene, as did 17[beta]-estradiol, while propylparaben upregulated both the extrinsic and intrinsic apoptotic pathways. There are differences in cell cycle and apoptosis gene expression between parabens and 17[beta]-estradiol in MCF-7 cells. In MCF-10A cells, most of the genes activated by parabens were comparable to those activated by 17[beta]-estradiol. Copyright © 2014 John Wiley & Sons, Ltd. Parabens are alkyl esters of p-hydroxybenzoic acid used as antimicrobial preservatives in pharmaceuticals, foods and cosmetics. The present study was undertaken to determine the effect of methyl, butyl- and propylparaben, and 17[beta]-estradiol as positive control, on cell cycle and apoptotic gene and protein expression in MCF-7 breast cancer and MCF-10A breast epithelial cells. The present results show differences between parabens and 17[beta]-estradiol mechanisms of action in MCF-7, while similar to that of 17[beta]-estradiol in non-transformed MCF-10A cells. [PUBLICATION ABSTRACT]