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

Cited 22 time in Web of Science Cited 23 time in Scopus
Authors
Kim, Dong-Seok; Lee, Hyun-Kyung; Park, Seo-Hyoung; Lee, Sangku; Ryoo, In-Ja; Kim, Won-Gon; Yoo, Ick-Dong; Na, Jung-Im; Kwon, Sun-Bang; Park, Kyoung-Chan
Issue Date
2007-11-06
Publisher
Wiley-Blackwell
Citation
Exp Dermatol. 2008; 17(4): 312-317
Keywords
Butadienes/pharmacologyCDC2 Protein Kinase/metabolismCell Cycle/*drug effects/physiologyCell Proliferation/*drug effectsCell Survival/drug effectsCells, CulturedCyclin B/metabolismCyclin-Dependent Kinase Inhibitor p27/metabolismCyclopentanes/*pharmacologyExtracellular Signal-Regulated MAP Kinases/antagonists & inhibitors/*metabolism/physiologyFlow CytometryHumansKeratinocytes/cytology/*drug effects/physiologyNitriles/pharmacologyPhosphorylationProtein Precursors/metabolismSignal Transduction/physiology
Abstract
Terrein, a fungal metabolite, has been recently shown to have a strong antiproliferative effect on skin equivalents. In the present study, we further investigated the effects of terrein on the possible signalling pathways involved in the growth inhibition of human epidermal keratinocytes by examining the regulations of extracellular signal-regulated protein kinase (ERK) and of the Akt pathway by terrein. It was observed that ERK was inactivated by terrein and that keratinocyte proliferation was inhibited, whereas Akt was unaffected. The inhibition of the ERK pathway by U0126 (a specific ERK inhibitor) also had a dose-dependent antiproliferative effect on human keratinocytes. These results indicate that ERK inhibition is involved in keratinocyte growth inhibition by terrein. Moreover, flow cytometric analysis showed that terrein inhibits DNA synthesis, as evidenced by a reduction in the S phase and an increase in the G2/M phase of the cell cycle. Thus, we next examined changes in the expressions of G2/M cell cycle-related proteins. Terrein was found to downregulate cyclin B1 and Cdc2 without Cdc2 phosphorylation, but upregulated p27(KIP1) (p27), a known inhibitor of cyclin-dependent kinase. These results suggest that terrein reduces human keratinocyte proliferation by inhibiting ERK and by decreasing the expressions of cyclin B1 and Cdc2 complex.
ISSN
1600-0625 (Electronic)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17979972

http://hdl.handle.net/10371/67529
DOI
https://doi.org/10.1111/j.1600-0625.2007.00646.x
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College of Medicine/School of Medicine (의과대학/대학원)Dermatology (피부과학전공)Journal Papers (저널논문_피부과학전공)
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