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Silybin and dehydrosilybin inhibit cytochrome P450 1A1 catalytic activity: A study in human keratinocytes and human hepatoma cells

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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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Abbreviations

CYP:

cytochrome P450

DH:

dehydrosilybin

DMSO:

dimethyl sulfoxide

EROD:

ethoxyresorufin-O-deethylase

FCS:

fetal calf serum

HaCaT:

human keratinocytes

HepG2:

human hepatoma cells

IC50:

50% inhibitory concentration

MTT:

3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyltetrazolium bromide

SB:

silybin

TCDD:

2,3,7,8-tetrachlorodibenzo-p-dioxin

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Authors and Affiliations

  1. Institute of Medical Chemistry and Biochemistry, Faculty of Medicine, Palacký University, Olomouc, Czech Republic

    Z. Dvořák, R. Vrzal & J. Ulrichová

  2. Institute of Medical Chemistry and Biochemistry, Faculty of Medicine, Palacký University Olomouc, Hněvotínská 3, 77515, Olomouc, Czech Republic

    Z. Dvořák

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  1. Z. Dvořák
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  2. R. Vrzal
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  3. J. Ulrichová
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Correspondence to Z. Dvořák.

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Dvořák, Z., Vrzal, R. & Ulrichová, J. Silybin and dehydrosilybin inhibit cytochrome P450 1A1 catalytic activity: A study in human keratinocytes and human hepatoma cells. Cell Biol Toxicol 22, 81–90 (2006). https://doi.org/10.1007/s10565-006-0017-0

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