Anti-tumor Effect of Oleic Acid in Hepatocellular Carcinoma Cell Lines via Autophagy Reduction

Abstract

Oleic acid (OA) is a component of the olive oil. Beneficial health effects of olive oil are well-known, such as protection against liver steatosis and against some cancer types. In the present study, we focused on OA effects in hepatocellular carcinoma (HCC), investigating responses to OA treatment (50–300 μM) in HCC cell lines (Hep3B and Huh7.5) and in a healthy liver-derived human cell line (THLE-2). Upon OA administration higher lipid accumulation, perilipin-2 increase, and autophagy reduction were observed in HCC cells as compared to healthy cells. OA in the presence of 10% FBS significantly reduced viability of HCC cell lines at 300 μM through Alamar Blue staining evaluation, and reduced cyclin D1 expression in a dose-dependent manner while it was ineffective on healthy hepatocytes. Furthermore, OA increased cell death by about 30%, inducing apoptosis and necrosis in HCC cells but not in healthy hepatocytes at 300 μM dosage. Moreover, OA induced senescence in Hep3B, reduced P-ERK in both HCC cell lines and significantly inhibited the antiapoptotic proteins c-Flip and Bcl-2 in HCC cells but not in healthy hepatocytes. All these results led us to conclude that different cell death processes occur in these two HCC cell lines upon OA treatment. Furthermore, 300 μM OA significantly reduced the migration and invasion of both HCC cell lines, while it has no effects on healthy cells. Finally, we investigated autophagy role in OA-dependent effects by using the autophagy inducer torin-1. Combined OA/torin-1 treatment reduced lipid accumulation and cell death as compared to single OA treatment. We therefore concluded that OA effects in HCC cells lines are, at least, in part dependent on OA-induced autophagy reduction. In conclusion, we report for the first time an autophagy dependent relevant anti-cancer effect of OA in human hepatocellular carcinoma cell lines.

Assessment of Biochemical Composition and Antioxidant Properties of Algerian Date Palm (Phoenix dactylifera L.) Seed Oil

“…Recent studies have shown that the most common monounsaturated fatty acid in the alimentary diet is oleic, which has protective effects against human diseases, in particular cardiovascular and inflammatory diseases, obesity, and some cancers [48][49][50]. The amounts of DPSO fatty acids reported in previous studies [14,27,31,[51][52][53] were, in general, very similar to the results obtained here.…”

Adipocytes Promote Breast Cancer Cell Survival and Migration through Autophagy Activation

“…The decrease in arachidonic acid content was responsible for autophagy activation in breast cancer cells by adipocytes. Specific fatty acids, depending on their unsaturation, were already linked with autophagy regulation, but results remain controversial for the same fatty acids in different models [22][23][24]. Interestingly, it has been demonstrated that unsaturated fatty acids induce a non-canonical form of autophagy, independent of Beclin1 but requiring the Golgi complex [33].…”

“…In general, lipids, mostly phospholipids, are associated with the regulation of autophagy since they are direct constituents of the autophagosome membrane, and they participate in the autophagosome formation and fusion with lysosomes, mainly through the regulation of the ubiquitin-like protein conjugation system leading to LC3 conjugation to phosphatidylethanolamine [15]. In addition, specific fatty acids, depending on their unsaturation, can regulate autophagy [22][23][24]. It has been demonstrated that free fatty acids derived from adipocytes induce AMPK activation in breast cancer cells [11], which is a major regulator of autophagy.…”

Commentary: Anti-tumor Effect of Oleic Acid in Hepatocellular Carcinoma Cell Lines via Autophagy Reduction

“…With great interest we read a paper "Anti-tumor Effect of Oleic Acid in Hepatocellular Carcinoma Cell Lines via Autophagy Reduction" published in Frontiers in Cell and Developmental Biology (Giulitti et al, 2021). Blocking autophagy suppresses the growth of HCC cells (Zai et al, 2020).…”