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Terrein inhibits keratinocyte proliferation via ERK inactivation and G2/M cell cycle arrest

Dong-Seok Kim1, Hyun-Kyung Lee, Seo-Hyoung Park

  • 1Department of Biochemistry, College of Medicine, Chung-Ang University, Republic of Korea.

Experimental Dermatology
|November 6, 2007
PubMed

Insights

The fungal metabolite terrein inhibits human keratinocyte proliferation by inactivating the extracellular signal-regulated kinase (ERK) pathway. This leads to cell cycle arrest and reduced DNA synthesis, revealing a novel mechanism for terrein

Area of Science:

  • Molecular Biology
  • Dermatology
  • Mycology

Background:

  • Terrene, a fungal metabolite, exhibits significant antiproliferative activity on skin equivalents.
  • Understanding the molecular mechanisms behind terrein's effects on human epidermal keratinocytes is crucial.

Purpose of the Study:

  • To investigate the signaling pathways, specifically extracellular signal-regulated protein kinase (ERK) and Akt, affected by terrein in human epidermal keratinocytes.
  • To elucidate the role of these pathways in terrein-induced growth inhibition.

Main Methods:

  • Treatment of human epidermal keratinocytes with terrein.
  • Analysis of ERK and Akt pathway activation using Western blotting.
  • Cell cycle analysis via flow cytometry.
  • Examination of cell cycle-related protein expression (cyclin B1, Cdc2, p27).

Main Results:

  • Terrene inactivated the ERK pathway, leading to keratinocyte proliferation inhibition; the Akt pathway remained unaffected.
  • Terrene treatment resulted in reduced DNA synthesis, with cells accumulating in the G2/M phase of the cell cycle.
  • Terrene downregulated cyclin B1 and Cdc2 expression while upregulating p27(KIP1), a cyclin-dependent kinase inhibitor.

Conclusions:

  • Extracellular signal-regulated kinase (ERK) pathway inhibition is a key mechanism by which terrein reduces human keratinocyte proliferation.
  • Terrene induces cell cycle arrest at the G2/M phase by modulating the expression of key cell cycle regulators.
  • These findings highlight terrein's potential as an antiproliferative agent targeting keratinocyte growth.

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