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.
Highlights
Hepatocellular carcinoma (HCC) is the fifth most prevalent malignancy worldwide, its incidence is rising [1,2]
A down-regulation of Fatty Acid Synthase (FAS) and HMG-CoAR gene expression was observed after eicosapentaenoic acid (EPA) and arachidonic acid (ARA) treatment in HepG2 cells, starting at 10 μM (P < 0.05, one-way analysis of variance (ANOVA) test and Dunnett’s post test)
Our results demonstrate that EPA and ARA inhibit HepG2 cell proliferation and induce apoptosis
Summary
Hepatocellular carcinoma (HCC) is the fifth most prevalent malignancy worldwide, its incidence is rising [1,2]. Gao et al [5] have demonstrated the in vitro efficacy of C75, a Fatty Acid Synthase (FAS) inhibitor that induces growth arrest in several HCC derived cell lines, offering a promising novel therapy that explores another frontier for hepatocellular cancer treatment, i.e. metabolic manipulation. FAS expression is markedly increased in several human cancers compared with the corresponding normal tissue and its overexpression in tumors has been associated with a poor prognosis [11,12]. Enhanced FAS expression is a poor prognostic factor in patients with breast, prostate, and ovarian cancer, generating an intriguing paradigm that cancers with high expression of FAS have a growth and/ or survival advantage and selective manipulation of FAS may be novel therapeutic strategy [14]
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