Document Detail


Inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity and of Ras farnesylation mediate antitumor effects of anandamide in human breast cancer cells.
MedLine Citation:
PMID:  20304978     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The endocannabinoid system regulates cell proliferation in human breast cancer cells. Recently, we described that a metabolically stable anandamide analog, 2-methyl-2'-F-anandamide, by activation of CB1 receptors significantly inhibited cell proliferation of human breast cancer cell lines. In this study, we observed that the activation of the CB1 receptor, in two human mammary carcinoma cell lines, MDA-MB-231 and MCF7, caused the inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase activity due to a reduction of HMG-CoA reductase transcript levels. The decrease of HMG-CoA reductase activity induced the inhibition of the prenylation of proteins, in particular of the farnesylation of Ras oncogenic protein involved in cell proliferation of these cell lines. We suggest that the inhibitory effect of anandamide analog on tumor cell proliferation could be related to the inhibition of Ras farnesylation.
Authors:
Chiara Laezza; Anna Maria Malfitano; Maria Chiara Proto; Iolanda Esposito; Patrizia Gazzerro; Pietro Formisano; Simona Pisanti; Antonietta Santoro; Maria Gabriella Caruso; Maurizio Bifulco
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-05-18
Journal Detail:
Title:  Endocrine-related cancer     Volume:  17     ISSN:  1479-6821     ISO Abbreviation:  Endocr. Relat. Cancer     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-05-20     Completed Date:  2010-09-13     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9436481     Medline TA:  Endocr Relat Cancer     Country:  England    
Other Details:
Languages:  eng     Pagination:  495-503     Citation Subset:  IM    
Affiliation:
Institute of Endocrinology e Experimental Oncology, CNR, Via Pansini 5, 80131 Naples, Italy. chilaez@libero.it
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MeSH Terms
Descriptor/Qualifier:
Alkyl and Aryl Transferases / antagonists & inhibitors*
Antineoplastic Agents / pharmacology
Arachidonic Acids / pharmacology*
Breast Neoplasms / genetics,  metabolism,  pathology*
Carcinoma / genetics,  metabolism,  pathology*
Cell Line, Tumor
Down-Regulation / drug effects
Drug Evaluation, Preclinical
Endocannabinoids / pharmacology
Enzyme Inhibitors / pharmacology
Female
Gene Expression Regulation, Enzymologic / drug effects
Gene Expression Regulation, Neoplastic / drug effects
Humans
Hydroxymethylglutaryl CoA Reductases / genetics,  metabolism
Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
Polyunsaturated Alkamides / pharmacology*
ras Proteins / genetics,  metabolism
Chemical
Reg. No./Substance:
0/2-methyl-2'-F-anandamide; 0/Antineoplastic Agents; 0/Arachidonic Acids; 0/Endocannabinoids; 0/Enzyme Inhibitors; 0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 0/Polyunsaturated Alkamides; 94421-68-8/anandamide; EC 1.1.1.-/Hydroxymethylglutaryl CoA Reductases; EC 2.5.-/Alkyl and Aryl Transferases; EC 2.5.1.-/geranylgeranyltransferase type-I; EC 3.6.5.2/ras Proteins

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


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