Antineoplastic effects of gamma linolenic Acid on hepatocellular carcinoma cell lines.

Journal of clinical biochemistry and nutrition ·Vol. 47 ·No. 1 ·2010-07-00 ·Pages 81-90

Itoh S, Taketomi A, Harimoto N, Tsujita E, Rikimaru T, Shirabe K, Shimada M, Maehara Y

Abstract

The aim of this study was to investigate the effect and the mechanism of gamma linolenic acid (GLA) treatment on human hepatocellular (HCC) cell lines. The human HCC cell line HuH7 was exposed to GLA. Cell proliferation and reactive oxygen species (ROS) generation including lipid peroxidation and apoptosis were compared. We then used a cDNA microarray analysis to investigate the molecular changes induced by GLA. GLA treatment significantly reduced cell proliferation, generated ROS, and induced apoptosis. After 24 h exposure of Huh7 cells to GLA, we identified several genes encoding the antioxidant proteins to be upregulated: heme oxygenase-1 (HO-1), aldo-keto reductase 1 family C1 (AKR1C1), C4 (AKR1C4), and thioredoxin (Trx). The HO-1 protein levels were overexpressed in Huh7 cells after GLA exposure using a Western blot analysis. Furthermore, chromium mesoporphyrin (CrMP), an inhibitor of HO activity, significantly potentiated GLA cytotoxicity. GLA treatment has induced cell growth inhibition, ROS generation including lipid peroxidation, and HO-1 production for antioxidant protection against oxidative stress caused by GLA in Huh7 cells. GLA treatment should be considered as a therapeutic modality in patients with advanced HCC.

Keywords

gamma linolenic acid heme oxygenase-1 hepatocellular carcinoma oxidant stress

Authors & Affiliations

8 authors, click to expand affiliations / ORCID

Itoh Shinji

Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.

Taketomi Akinobu

Harimoto Norifumi

Tsujita Eiji

Rikimaru Tatsuya

Shirabe Ken

Shimada Mitsuo

Maehara Yoshihiko

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Article Info

Journal

Journal of clinical biochemistry and nutrition

Abbr.

J Clin Biochem Nutr

ISSN

1880-5086

DOI

10.3164/jcbn.10-24

Published

2010-07-00

Epub

2010-00-22

Pages

81-90

Language

English

Region

Japan

NLM ID

8700907

PMCID

PMC2901768

External Links

PubMed source DOI: 10.3164/jcbn.10-24 PMC Full Text View journal details

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Antineoplastic effects of gamma linolenic Acid on hepatocellular carcinoma cell lines.

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