Document Detail

Rottlerin: a multifaced regulator of keratinocyte cell cycle.
MedLine Citation:
PMID:  19492998     Owner:  NLM     Status:  MEDLINE    
In this study we showed that Rottlerin (also called Kamala or Mallotoxin), a natural product purified from Mallotus phillippinensis, is a potent suppressor of human keratinocytes (HaCaT cell line) proliferation. Following Rottlerin treatment, Thymidine incorporation into DNA and re-epithelialisation in a scratch wound model was decreased. At the molecular level, Rottlerin hampered the NFkB activation process, causing loss of cyclin D1 and promoting, in a PKCdelta-dependent pathway, ERK activation, which, in turn induced the cell cycle inhibitor p21 Cip1/Kip1. The NFkB-dependent drop in cyclin D1, along with the PKCdelta/ERK-dependent induction of p21 Cip1/Kip1, is responsible for growth arrest. These results open the way to further investigation on the Rottlerin therapeutic potential against keratinocyte hyper-proliferative disorders.
Giuseppe Valacchi; Alessandra Pecorelli; Marzia Mencarelli; Paola Carbotti; Vittoria Fortino; Michela Muscettola; Emanuela Maioli
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Experimental dermatology     Volume:  18     ISSN:  1600-0625     ISO Abbreviation:  Exp. Dermatol.     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-06-04     Completed Date:  2009-08-25     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9301549     Medline TA:  Exp Dermatol     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  516-21     Citation Subset:  IM    
Department of Biomedical Sciences, University of Siena, Siena, Italy.
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MeSH Terms
Acetophenones / pharmacology*
Active Transport, Cell Nucleus / drug effects
Benzopyrans / pharmacology*
Cell Cycle / drug effects
Cell Line, Transformed / drug effects
Cells, Cultured / cytology,  drug effects
Cyclin D1 / biosynthesis
Cyclin D2
Cyclin-Dependent Kinase Inhibitor p21 / biosynthesis,  genetics
Cyclins / biosynthesis,  genetics
Drug Evaluation, Preclinical
Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors,  metabolism
Gene Expression Regulation / drug effects
Genes, bcl-1 / drug effects
Growth Inhibitors / pharmacology*
Keratinocytes / cytology,  drug effects*
NF-kappa B / antagonists & inhibitors
Phosphorylation / drug effects
Protein Kinase C-delta / antagonists & inhibitors,  physiology
Protein Kinase Inhibitors / pharmacology*
Protein Processing, Post-Translational / drug effects
Wound Healing / drug effects
Reg. No./Substance:
0/Acetophenones; 0/Benzopyrans; 0/CCND1 protein, human; 0/CCND2 protein, human; 0/CDKN1A protein, human; 0/Cyclin D2; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Cyclins; 0/Growth Inhibitors; 0/NF-kappa B; 0/Protein Kinase Inhibitors; 136601-57-5/Cyclin D1; 82-08-6/rottlerin; EC Kinase C-delta; EC Signal-Regulated MAP Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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