Eicosapentaenoic acid inhibits cell growth and triacylglycerol secretion in McA-RH7777 rat hepatoma cultures

Abstract

The plasma triacylglycerol-decreasing effect of fish-oil fatty acids was studied in vitro by using the rapidly growing cultured rat hepatoma cell line McA-RH7777. Cells were exposed to albumin-complexed eicosapentaenoic acid (C20:5n-3; EPA), to oleic acid (C18:1n-9; OA), or to albumin alone. Cell growth was similar in albumin- and OA-supplemented cultures, but EPA treatment inhibited growth. As estimated by [14C]glycerol incorporation, OA stimulated both net triacylglycerol synthesis and secretion over control levels in a dose-dependent manner. EPA stimulated triacylglycerol synthesis in similar fashion to OA, but paradoxically decreased net triacylglycerol secretion and led to exaggerated intracellular accumulation of radiolabelled triacylglycerol. The EPA and OA effects were additive at low concentrations of total fatty acid, but at higher fatty acid concentrations OA appeared to negate some effects of EPA. Chemical analysis of albumin- and OA-treated cultures revealed OA-dominant profiles for both cellular and medium triacylglycerol-associated fatty acids. In contrast, EPA was the principal fatty acid in cellular triacylglycerol of EPA-supplemented cultures, whereas medium triacylglycerol from these cultures contained very little EPA. We conclude that McA-RH7777 hepatoma cells readily synthesize EPA-containing triacylglycerol molecules, but they have variable capacity for secreting them. We consider potential mechanisms to account for the effects of EPA in this system.

Eicosapentaenoic acid ameliorates steatohepatitis and hepatocellular carcinoma in hepatocyte-specific Pten-deficient mice

“…There have been some investigations of the anticancer effect of EPA on hepatoma cell lines [34][35][36][37], implanted [38][39][40], and diethylnitrosamine-induced hepatoma [41]. In this context, our present study is the first to demonstrate that EPA inhibits HCC in steatohepatitis.…”

“…In this context, our present study is the first to demonstrate that EPA inhibits HCC in steatohepatitis. Previous studies revealed that the mechanism underlying the cytotoxicity of EPA to hepatoma cells was ascribed to either induction of cell death or inhibition of cell proliferation [34][35][36][37][38][39][40]. In 40-week-old Pten KO mice, EPA administration was not responsible for apoptosis but rather inhibiting proliferation of precancerous hepatocytes, as demonstrated by PCNA nuclear staining.…”

Myristic acid increases dense lipoprotein secretion by inhibiting apoB degradation and triglyceride recruitment

“…2B, while all three fatty acids increased secretion of labeled TG (compared with the results from incubation with BSA alone), the greatest increase was seen with OA ( ‫ف‬ 3 ϫ greater, P Ͻ 0.01). As reported by us and others (17,25), relative to the results with OA, incubation of McA cells with an n-3 fatty acid resulted in decreased secretion of labeled TG, but, surprisingly, so did incubation with MA ( P Ͻ 0.01 for either DHA or MA vs. OA). Because of this unexpected result, we wished to further explore the effects of MA that led to increased apoB-100 secretion and decreased TG secretion.…”

Lipids changes in liver cancer

“…Keler et al(1992) showed that dietary linoleic acid increases hepatoma growth. Fish oil was found to inhibit hepatic carcinogenesis (Ramesh and Das, 1995) and decrease growth (Fox and Hay, 1992). It is probable that this effect of linoleic acid is mediated through prostaglandin E2 (PGE2).…”