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.
Chang, Y.-C.; Huang, Y.-H.; Shih, C.-M.; Wu, J.-Y.; Liu, C.-L.; Wang, S.-H.; and Lin, C.-M.
"Down-regulation of fatty acid synthase is associated with decreased Akt activation in lovastatin induced apoptosis cells,"
Journal of Food and Drug Analysis: Vol. 14
, Article 5.
Available at: https://doi.org/10.38212/2224-6614.2454