title: Action of methyl-, propyl- and butylparaben on GPR30 gene and protein expression, cAMP levels and activation of ERK1/2 and PI3K/Akt signaling pathways in MCF-7 breast cancer cells and MCF-10A non-transformed breast epithelial cells.
abstract: In the present study, we examined cAMP levels and activation of the MAPK/ERK1/2 and PI3K/Akt signaling pathways in response to the actions of parabens on GPR30 in MCF-7 and MCF-10A cells. Cells were exposed to methyl-, propyl- or butylparaben at a concentration of 20nM; 17-β-estradiol (10nM) was used as a positive control. 17β-estradiol and all tested parabens increased GPR30 gene and protein expression in MCF-7 and MCF-10A cells. No parabens affected cAMP levels in either cell line, with the exception of propylparaben in MCF-10A cells. 17β-estradiol, propylparaben, and butylparaben increased phosphorylation of ERK1/2 in MCF-7 cells, whereas 17β-estradiol, methyl- and butylparaben, but not propylparaben, increased phosphorylation of ERK1/2 in MCF-10A cells. Akt activation was noted only in MCF-7 cells and only with propylparaben treatment. Collectively, the data presented here point to a nongenomic mechanism of action of parabens in activation GPR30 in both cancer and non-cancer breast cell lines through βγ dimer-mediated activation of the ERK1/2 pathway, but not the cAMP/PKA pathway. Moreover, among investigated parabens, propylparaben appears to inhibit apoptosis in cancer cells through activation of Akt kinases, confirming conclusions suggested by our previously published data. Nevertheless, continuing research on the carcinogenic action of parabens is warranted.
authors.affiliation: Department of Physiology and Toxicology of Reproduction, Institute of Zoology, Jagiellonian University in Kraków, Gronostajowa 9, 30-387 Krakow, Poland. Electronic address: ania.wrobel@uj.edu.pl.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Wróbel
authors.affiliation: Department of Physiology and Toxicology of Reproduction, Institute of Zoology, Jagiellonian University in Kraków, Gronostajowa 9, 30-387 Krakow, Poland. Electronic address: ewa.gregoraszczuk@uj.edu.pl.
authors.forename: Ewa Łucja
authors.initials: EŁ
authors.lastname: Gregoraszczuk
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D000242:Cyclic AMP / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D042361:Mammary Glands, Human / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D010226:Parabens / Q000633:toxicity*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D015854:Up-Regulation
chemical_list: C109584:GPER1 protein, human; D010226:Parabens; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; C038091:butylparaben; D004958:Estradiol; C015358:methylparaben; D000242:Cyclic AMP; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C006068:propylparaben
keywords: Breast cancer; GPR30; Non-genomic action; Parabens; cAMP