title: Methylparaben-induced decrease in collagen production and viability of cultured human dermal fibroblasts.
abstract: Parabens owing to their many advantageous properties are widely applied in cosmetics, food products and pharmaceuticals. However, recent research results have shown that they possess the ability to accumulate in the human body and exert many adverse effects. In this study, the impact of methylparaben (MP) as the most frequently used preservative in cosmetics, on human dermal fibroblasts and collagen production was evaluated. In cells treated with 0.01, 0.03 and 0.05% MP a dose-dependent decrease in collagen biosynthesis was revealed, which was positively correlated with the activity of prolidase responsible for the recovery of proline. Consequently, the concentration of total collagen secreted into the medium was markedly diminished. A similar reduction in expression of the major skin collagen type I at both the protein and mRNA level as well as collagen type III and VI at the mRNA level was also detected. The decrease in the collagen level may result not only from the reduced synthesis but also increased degradation owing to MP-induced activation of pro-MMP-2 (72 kDa). The increase in activity of MMP-2 (66 kDa) was accompanied by a reduction in the inhibitory activity of TIMP-2. In addition, an inhibitory effect of MP on cell survival and proliferation was revealed in this study. The increased expression and nuclear translocation of caspase-3 as well as increased Bax and decreased Bcl-2 expression may suggest MP-induced cell apoptosis. In summary, we have provided new data on the adverse effects of methylparaben on human dermal fibroblasts and the main structural protein of the skin. Further studies on the mechanisms responsible for its action are in progress. Copyright © 2017 John Wiley & Sons, Ltd.
authors.affiliation: Department of Medical Chemistry, Medical University of Bialystok, Kilinskiego 1, 15-230, Bialystok, Poland.
authors.forename: Natalia
authors.initials: N
authors.lastname: Majewska
authors.affiliation: Department of Medicinal Chemistry, Medical University of Bialystok, Kilinskiego 1, 15-230, Bialystok, Poland.
authors.forename: Ilona
authors.initials: I
authors.lastname: Zaręba
authors.affiliation: Department of Medicinal Chemistry, Medical University of Bialystok, Kilinskiego 1, 15-230, Bialystok, Poland.
authors.forename: Arkadiusz
authors.initials: A
authors.lastname: Surażyński
authors.affiliation: Department of Medical Chemistry, Medical University of Bialystok, Kilinskiego 1, 15-230, Bialystok, Poland.
authors.forename: Anna
authors.identifier: 0000-0002-4027-989X
authors.initials: A
authors.lastname: Galicka
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004792:Enzyme Precursors / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D018093:Gelatinases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D010226:Parabens / Q000633:toxicity*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000187:drug effects; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C494826:BAX protein, human; D004792:Enzyme Precursors; D010226:Parabens; D012333:RNA, Messenger; C560822:TIMP1 protein, human; C560823:TIMP2 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D051028:bcl-2-Associated X Protein; D019716:Tissue Inhibitor of Metalloproteinase-2; D003094:Collagen; C015358:methylparaben; C505407:CASP3 protein, human; D053148:Caspase 3; D018093:Gelatinases; C069860:progelatinase; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2
keywords: MMP-2; TIMP-2; apoptosis; collagen; methylparaben; prolidase; proliferation; viability