PKCι is a target of 7,8,4'-trihydroxyisoflavone for the suppression of UVB-induced MMP-1 expression

Exp Dermatol. 2018 May;27(5):449-452. doi: 10.1111/exd.13375. Epub 2017 Jul 10.

Abstract

The soy isoflavone daidzein is bioconverted to 7,8,4'-trihydroxyisoflavone (7,8,4'-THIF) by microorganisms. Here, we investigated the matrix metalloproteinase (MMP)-1 inhibitory properties of 7,8,4'-THIF that arise through the suppression of UVB-induced MMP-1 expression. 7,8,4'-THIF reduced UVB-induced MMP-1 expression at the transcriptional level in primary human dermal fibroblasts and inhibited UVB-induced transcriptional activity of AP-1, a major activator of MMP-1 expression. Additionally, it was observed that the mitogen-activated protein kinase (MAPK) pathway, a crucial signalling cascade for MMP-1 expression, was suppressed by 7,8,4'-THIF. Protein kinase C iota (PKCι) was suspected to be a direct target of 7,8,4'-THIF. The direct interaction between 7,8,4'-THIF and PKCι was confirmed using pull-down assays and immobilized metal ion affinity-based fluorescence polarization assays. Finally, we observed that 7,8,4'-THIF inhibited UVB-induced MMP-1 expression in a human skin equivalent model. Taken together, these results suggest that 7,8,4'-THIF, a bioconversion product of daidzein, suppresses UVB-induced MMP-1 expression.

Keywords: 3D culture; 7,8,4′-trihydroxyisoflavone; Protein kinase C iota; matrix metalloproteinase-1.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Drug Evaluation, Preclinical
  • Humans
  • Isoenzymes / antagonists & inhibitors*
  • Isoflavones / pharmacology*
  • Matrix Metalloproteinase 1 / metabolism*
  • Protein Kinase C / antagonists & inhibitors*
  • Skin Aging / drug effects
  • Ultraviolet Rays

Substances

  • 7,8,4'-trihydroxyisoflavone
  • Isoenzymes
  • Isoflavones
  • Protein Kinase C
  • protein kinase C lambda
  • MMP1 protein, human
  • Matrix Metalloproteinase 1