Decrease of human hepatoma cell growth by arachidonic acid is associated with an accumulation of derived products from lipid peroxidation
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- 作者：Bianchi ; Arnaud ; Dewailly ; Etienne ; Gautier ; Hervé ; Merlin ; Jean Louis ; Slomianny ; Christian ; et. al.
- 关键词：Arachidonic acid ; Oxidative stress ; Lipid peroxidation ; Cell growth ; HepG2 cells ; AA ; Arachidonic acid ; AIP ; 1 amino-3-iminopropene bridges ; AP-1 ; activator protein-1 ; Cu/ZnSOD ; copper/zinc-dependent superoxide dismutase ; ETYA ; 5 ; 8 ; 11 ; 14-eicosatetraynoic
- 刊名：Biochimie
- 出版年：2004
- 出版时间：September - October, 2004
- 年：2004
- 卷：86
- 期：9-10
- 页码：633-642
- 全文大小：388 K
文摘
We showed that the metabolism of arachidonic acid (AA) in HepG2 cells generates reactive oxygen species (ROS), which activate the p38 mitogen-activated protein kinase (MAPK) pathway and the redox-sensitive transcription factors AP-1 and NF-κB, leading to the induction of the antioxidant manganese superoxide dismutase gene. The present study reports that AA decreases the HepG2 cell growth by 40 % and 55 % after a treatment for 24 and 48 h, respectively. This effect was blocked by an inhibitor of lipoxygenase/cytochrome P450 monooxygenase pathways and by the antioxidants. In addition, AA induced an oxidative stress, as an accumulation of malondialdehyde (MDA)-modified proteins, resulting to a generation of MDA and H2O2 was observed after 24 h. This AA-induced oxidative stress was associated with the lack of an increase in the H2O2-degrading enzyme level. In contrast, 5,8,11,14-eicosatetraynoic acid, a nonmetabolizable analog of AA, had not effect. The peroxisome proliferator-activated receptor gamma (PPARγ) with AA metabolites as ligands was upregulated by the fatty acid but was not involved in the AA effect because its transcriptional activity estimated by reporter gene assays was negatively controlled by p38 MAPK pathway. These findings suggest that the effect of AA on human hepatoma cell growth by inducing an oxidative stress may present a clinical interest in the treatment of the liver cancer.