Antineoplastic effects of gamma linolenic acid on hepatocellular carcinoma cell lines

Shinji Itoh, Akinobu Taketomi, Norifumi Harimoto, Eiji Tsujita, Tatsuya Rikimaru, Ken Shirabe, Mitsuo Shimada, Yoshihiko Maehara

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)81-90
Number of pages10
JournalJournal of Clinical Biochemistry and Nutrition
Issue number1
Publication statusPublished - Jul 2010

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Nutrition and Dietetics
  • Clinical Biochemistry


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