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 (20 nm) or 17β-estradiol (10 nm). Cell cycle and apoptotic gene expression were evaluated by real-time polymerase chain reaction and
protein expression by Western blot. 17β-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 17β-estradiol, while
propylparaben upregulated both the extrinsic and intrinsic apoptotic pathways. There are differences in cell cycle and apoptosis gene expression between
parabens and 17β-estradiol in MCF-7 cells. In MCF-10A cells, most of the genes activated by
parabens were comparable to those activated by 17β-estradiol.