Differential effect of methyl-, butyl- and propylparaben and 17β-estradiol on selected cell cycle and apoptosis gene and protein expression in MCF-7 breast cancer cells and MCF-10A non-malignant cells.
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.
Department of Physiology and Toxicology of Reproduction Institute of Zoology, Jagiellonian University in Kraków, Gronostajowa 9, 30-387, Krakow, Poland.
Anna Maria
AM
Wróbel
Ewa Łucja
EŁ
Gregoraszczuk
D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D004958:Estradiol / Q000633:toxicity*; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D010226:Parabens / Q000633:toxicity*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; C494811:BCL2L1 protein, human; C491073:BCL2L2 protein, human; D010226:Parabens; D012333:RNA, Messenger; D051020:bcl-X Protein; C038091:butylparaben; D004958:Estradiol; C015358:methylparaben; C506433:CASP9 protein, human; D053453:Caspase 9; C006068:propylparaben
apoptosis; breast cancer; cell cycle; parabens