Polyunsaturated fatty acids reduce Fatty Acid Synthase and Hydroxy-Methyl-Glutaryl CoA-Reductase gene expression and promote apoptosis in HepG2 cell line

Abstract

Backgroundn-3 and n-6 polyunsaturated fatty acids (PUFAs) are the two major classes of PUFAs encountered in the diet, and both classes of fatty acids are required for normal human health. Moreover, PUFAs have effects on diverse pathological processes impacting chronic disease, such as cardiovascular and immune disease, neurological disease, and cancer.AimTo investigate the effects of eicosapentaenoic acid (EPA) and arachidonic acid (ARA) on the proliferation and apoptosis of human hepatoma cell line HepG2 after exposure to increasing concentrations of EPA or ARA for 48 h. Moreover, in the same cells the gene expression of Fatty Acid Synthase (FAS) and 3-Hydroxy-3-Methyl-Glutaryl Coenzyme A Reductase (HMG-CoAR) was also investigated.MethodCell growth and apoptosis were assayed by MTT and ELISA test, respectively after cell exposure to increasing concentrations of EPA and ARA. Reverse-transcription and real-time PCR was used to detect FAS and HMG-CoAR mRNA levels in treated cells.ResultsOur findings show that EPA inhibits HepG2 cell growth in a dose-dependent manner, starting from 25 μM (P < 0.01, one-way ANOVA test and Dunnett's post test) and exerts a statistically significant pro-apoptotic effect already at 1 μM of EPA. Higher doses of ARA were need to obtain a statistically significant inhibition of cell proliferation and a pro-apoptotic effect in these cells (100 μM, P < 0.01, one-way ANOVA test and Dunnett's post test). Moreover, a down-regulation of FAS and HMG-CoAR gene expression was observed after EPA and ARA treatment in HepG2 cells, starting at 10 μM (P < 0.05, one-way ANOVA test and Dunnett's post test).ConclusionOur results demonstrate that EPA and ARA inhibit HepG2 cell proliferation and induce apoptosis. The down-regulation of FAS and HMG-CoAR gene expression by EPA and ARA might be one of the mechanisms for the anti-proliferative properties of PUFAs in an in vitro model of hepatocellular carcinoma.

Dietary ω-3 Polyunsaturated Fatty Acids Inhibit Tumor Growth in Transgenic ApcMin/+ Mice, Correlating with CB1 Receptor Up-Regulation

“…PUFAs can inhibit colon carcinogenesis, affecting tumor progression [3]. Previously, we showed the ability of ω-3 PUFAs to arrest cell growth and to promote cell apoptosis in animal and in vitro studies [4,5,6]. Moreover, ω-3 PUFAs ingested in the diet were also able to significantly reverse polyp development in Apc Min/+ mice through inducing the estrogen receptor β and Low Density Lipoprotein (LDL) receptor [7], known to be negative modulators of cell proliferation.…”

Blocking fatty acid synthase inhibits tumor progression of human osteosarcoma by regulating the human epidermal growth factor receptor 2/phosphoinositide 3-kinase/protein kinase B signaling pathway in xenograft models

“…Research has demonstrated that FASN is overexpressed in various human tumors and FASN has been identified as a crucial factor for sustaining a number of biological features of cancer cells (5)(6)(7)(8)(9). Inhibition of FASN may suppress cancer cell proliferation and metastasis in vitro and in vivo (10)(11)(12)(13)(14). Previous studies have demonstrated that FASN is overexpressed in OS cells and tissues and knockdown of FASN may suppresses the invasion and migratory ability of OS cells by downregulating the human epidermal growth factor receptor 2 (HER2)/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/nuclear factor (NF)-κB signaling pathway in vitro (15,16); however, the tumor microenvironment has an important influence on tumor progression.…”

microRNA-195 suppresses osteosarcoma cell invasion and migration in vitro by targeting FASN

“…FASN is expressed at high levels in a variety of human tumors (11)(12)(13)(14), but exists at low levels in normal tissues. Various studies have reported that the inhibition of FASN expression suppresses cancer cell proliferation in vitro and in vivo (15)(16)(17)(18)(19)(20). Thus, FASN is considered a novel promising target for anticancer therapy.…”