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

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...

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Autores principales: Giulitti, Federico, Petrungaro, Simonetta, Mandatori, Sara, Tomaipitinca, Luana, de Franchis, Valerio, D'Amore, Antonella, Filippini, Antonio, Gaudio, Eugenio, Ziparo, Elio, Giampietri, Claudia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892977/
https://www.ncbi.nlm.nih.gov/pubmed/33614661
http://dx.doi.org/10.3389/fcell.2021.629182
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author Giulitti, Federico
Petrungaro, Simonetta
Mandatori, Sara
Tomaipitinca, Luana
de Franchis, Valerio
D'Amore, Antonella
Filippini, Antonio
Gaudio, Eugenio
Ziparo, Elio
Giampietri, Claudia
author_facet Giulitti, Federico
Petrungaro, Simonetta
Mandatori, Sara
Tomaipitinca, Luana
de Franchis, Valerio
D'Amore, Antonella
Filippini, Antonio
Gaudio, Eugenio
Ziparo, Elio
Giampietri, Claudia
author_sort Giulitti, Federico
collection PubMed
description 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.
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spelling pubmed-78929772021-02-20 Anti-tumor Effect of Oleic Acid in Hepatocellular Carcinoma Cell Lines via Autophagy Reduction Giulitti, Federico Petrungaro, Simonetta Mandatori, Sara Tomaipitinca, Luana de Franchis, Valerio D'Amore, Antonella Filippini, Antonio Gaudio, Eugenio Ziparo, Elio Giampietri, Claudia Front Cell Dev Biol Cell and Developmental Biology 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. Frontiers Media S.A. 2021-02-05 /pmc/articles/PMC7892977/ /pubmed/33614661 http://dx.doi.org/10.3389/fcell.2021.629182 Text en Copyright © 2021 Giulitti, Petrungaro, Mandatori, Tomaipitinca, de Franchis, D'Amore, Filippini, Gaudio, Ziparo and Giampietri. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Giulitti, Federico
Petrungaro, Simonetta
Mandatori, Sara
Tomaipitinca, Luana
de Franchis, Valerio
D'Amore, Antonella
Filippini, Antonio
Gaudio, Eugenio
Ziparo, Elio
Giampietri, Claudia
Anti-tumor Effect of Oleic Acid in Hepatocellular Carcinoma Cell Lines via Autophagy Reduction
title Anti-tumor Effect of Oleic Acid in Hepatocellular Carcinoma Cell Lines via Autophagy Reduction
title_full Anti-tumor Effect of Oleic Acid in Hepatocellular Carcinoma Cell Lines via Autophagy Reduction
title_fullStr Anti-tumor Effect of Oleic Acid in Hepatocellular Carcinoma Cell Lines via Autophagy Reduction
title_full_unstemmed Anti-tumor Effect of Oleic Acid in Hepatocellular Carcinoma Cell Lines via Autophagy Reduction
title_short Anti-tumor Effect of Oleic Acid in Hepatocellular Carcinoma Cell Lines via Autophagy Reduction
title_sort anti-tumor effect of oleic acid in hepatocellular carcinoma cell lines via autophagy reduction
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892977/
https://www.ncbi.nlm.nih.gov/pubmed/33614661
http://dx.doi.org/10.3389/fcell.2021.629182
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