Down-regulation of fatty acid synthase is associated with decreased Akt activation in lovastatin induced apoptosis cells

Yuan Ching Chang, Yen Hua Huang, Chwen Ming Shih, Jui Yu Wu, Chien Liang Liu, Shwu Huey Wang, Chun Mao Lin

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Increased fatty acid synthase (FAS) protein expression is coordinated with cancer development. FAS inhibitors become a focus of anticancer drug development. Lovastatin, one of the active ingredients in red yeast rice, is a product of Monascus purpureus. Lovastatin has been shown to inhibit proliferation and to induce apoptosis in a variety of tumor cells. This report shows that chemopreventive effects of lovastatin may be through the down regulation of FAS. Lovastatin exhibited significant apoptosis-inducing activity in HL-60 cells, as observed by flow cytometry (with 49.83% in sub-GI peak compared to the control, 10.43%), blebbing cell membrane morphology, and nuclear condensation. Cellular triglyceride, cholesterol, and free fatty acid in HepG2 cells were reduced to 79%, 81%, and 75%, respectively, upon lovastatin treatment (50 μM) for 4 h. The relative levels of FAS protein after treatment with 0, 10, 20, and 50 μM lovastatin were 1.00, 0.89, 0.72, and 0.31, respectively. Phosphorylated Akt was reduced in a dose-dependent manner. Reverse transcription PCR analysis showed that lovastatin upregulated PPAR-γ and inhibited SREBP-1 mRNA expression in HepG2 cells. Our current results implicate that lovastatin inhibiting FAS expression is associated with the decreased Akt activation.

Original languageEnglish
Pages (from-to)340-345
Number of pages6
JournalJournal of Food and Drug Analysis
Volume14
Issue number4
Publication statusPublished - Dec 2006

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Keywords

  • Fatty acid synthase
  • Lovastatin
  • PKB/Akt
  • PPAR
  • SREBP
  • Statin

ASJC Scopus subject areas

  • Food Science
  • Pharmacology

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