Inhibition of 3-hydroxy-3-methylglutarylcoenzyme a reductase activity and of Ras farnesylation mediate antitumor effects of anandamide in human breast cancer cells

Chiara Laezza, Anna Maria Malfitano, Maria Chiara Proto, Iolanda Esposito, Patrizia Gazzerro, Pietro Formisano, Simona Pisanti, Antonietta Santoro, Maria Gabriella Caruso, Maurizio Bifulco

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)495-503
Number of pages9
JournalEndocrine-Related Cancer
Volume17
Issue number2
DOIs
Publication statusPublished - Jun 2010

    Fingerprint

ASJC Scopus subject areas

  • Endocrinology
  • Oncology
  • Cancer Research
  • Endocrinology, Diabetes and Metabolism

Cite this