Silybin and dehydrosilybin inhibit cytochrome P450 1A1 catalytic activity: A study in human keratinocytes and human hepatoma cells |
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Authors: | Z Dvo?ák R Vrzal J Ulrichová |
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Institution: | (1) Institute of Medical Chemistry and Biochemistry, Faculty of Medicine, Palacky University, Olomouc, Czech Republic;(2) Institute of Medical Chemistry and Biochemistry, Faculty of Medicine, Palacky University Olomouc, Hněvotínská 3, 77515 Olomouc, Czech Republic |
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Abstract: | The flavonolignan silybin and its derivative dehydrosilybin have been proposed as candidate UV-protective agents in skin care
products. This study addressed the effect of silybin and dehydrosilybin on the activity of cytochrome P450 isoform CYP1A1
in human keratinocytes (HaCaT) and human hepatoma cells (HepG2). CYP1A1 catalytic activity was assessed as O-deethylation of 7-ethoxyresorufin using fluorescence detection. Silybin and dehydrosylibin inhibited basal and dioxin-inducible
CYP1A1 catalytic activity in both cell lines used. The inhibitory effect of tested compounds was more pronounced in HaCaT
cells than in HepG2 cells, and dehydrosilybin was a much stronger inhibitor than silybin. Analyses on CYP1A1 human recombinant
protein yielded IC50 values of 22.9 ± 4.7 μmol/L and 0.43 ± 0.04 μmol/L for silybin and dehydrosilybin, respectively. Since CYP1A enzymes are
some of the most prominent actors in the process of chemically induced carcinogenesis, the inhibitory activity of the flavonolignans
tested against CYP1A1 favors their use as cytoprotective agents in terms of skin and hepatic metabolism. In addition, the
capability of dehydrosilybin to inhibit CYP1A1 in submicromolar concentrations makes this compound a potential biological
probe in CYP1A1 analyses. |
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Keywords: | CYP1A1 dehydrosilybin enzyme inhibition HaCaT cells HepG2 cells |
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