Isoprocurcumenol Supports Keratinocyte Growth and Survival through Epidermal Growth Factor Receptor Activation

Int J Mol Sci. 2021 Nov 22;22(22):12579. doi: 10.3390/ijms222212579.

Abstract

Although proliferation of keratinocytes, a major type of skin cells, is a key factor in maintaining the function of skin, their ability to proliferate tends to diminish with age. To solve such a problem, researchers in medical and skin cosmetic fields have tried to utilize epidermal growth factor (EGF), but achieved limited success. Therefore, a small natural compound that can mimic the activity of EGF is highly desired in both medical and cosmetic fields. Here, using the modified biosensor system, we observed that natural small-compound isoprocurcumenol, which is a terpenoid molecule derived from turmeric, can activate EGFR signaling. It increased the phosphorylation of ERK and AKT, and upregulated the expression of genes related to cell growth and proliferation, such as c-myc, c-jun, c-fos, and egr-1. In addition, isoprocurcumenol induced the proliferation of keratinocytes in both physical and UVB-induced cellular damage, indicative of its function in skin regeneration. These findings reveal that EGF-like isoprocurcumenol promotes the proliferation of keratinocytes and further suggest its potential as an ingredient for medical and cosmetics use.

Keywords: EGFR signaling; isoprocurcumenol; keratinocyte; natural compound; wound healing.

MeSH terms

  • Cell Line
  • Cell Proliferation / drug effects*
  • Epidermal Growth Factor / genetics
  • ErbB Receptors / genetics
  • Humans
  • JNK Mitogen-Activated Protein Kinases / genetics
  • Keratinocytes / metabolism
  • MAP Kinase Signaling System / drug effects
  • Phosphorylation / drug effects
  • Protein Binding / genetics
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-fos / genetics
  • Proto-Oncogene Proteins c-myc / genetics
  • Regeneration / drug effects*
  • Sesquiterpenes / chemistry
  • Sesquiterpenes / pharmacology*
  • Signal Transduction / drug effects
  • Skin / growth & development
  • Skin / metabolism
  • Transcriptional Activation / drug effects*
  • Wound Healing / drug effects

Substances

  • MYC protein, human
  • Proto-Oncogene Proteins c-fos
  • Proto-Oncogene Proteins c-myc
  • Sesquiterpenes
  • procurcumenol
  • Epidermal Growth Factor
  • EGFR protein, human
  • ErbB Receptors
  • Proto-Oncogene Proteins c-akt
  • JNK Mitogen-Activated Protein Kinases