12-lipoxygenase inhibition induced apoptosis in human gastric cancer cells

被引：93

作者：

Wong, BCY ^{[1
]}

Wang, WP

Cho, CH

Fan, XM

Lin, MCM

Kung, HF

Lam, SK

机构：

[1] Univ Hong Kong, Dept Med, Hong Kong, Hong Kong, Peoples R China

[2] Univ Hong Kong, Dept Pharmacol, Hong Kong, Hong Kong, Peoples R China

[3] Univ Hong Kong, Inst Mol Biol, Hong Kong, Hong Kong, Peoples R China

来源：

CARCINOGENESIS | 2001年 / 22卷 / 09期

关键词：

D O I：

10.1093/carcin/22.9.1349

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Arachidonic acid release from membrane phospholipids is essential for tumour cell proliferation. Lipoxygenases constitute a pathway for arachidonate metabolism. The present study investigated the expression of 12-lipoxygenase and its effect on cell proliferation as well as survival in two human gastric cancer cell lines (AGS and MKN-28). RT-PCR and western blots, respectively, showed 12-LOX mRNA and protein expression in both AGS and MKN-28 cell lines. Treatment with a 12-LOX inhibitor, baicalein, significantly inhibited cancer cell proliferation, but a metabolite of 12-LOX activity, 12 hydroxyeicosatetraenoic acid (12-HETE) reversed baicalein-induced growth inhibition. Furthermore, the blockade of the 12-LOX pathway through a 12-LOX inhibitor and antisense induced apoptosis of gastric cancer cell lines. The biochemical characteristics of apoptosis were p53-independent combined with a decrease in bcl-2 expression. Caspase-7 was proteolytically activated and responsible for the apoptosis execution.

引用

页码：1349 / 1354

页数：6

共 40 条

[1] Lipoxygenases: Occurrence, functions, catalysis, and acquisition of substrate [J].

Brash, AR .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (34) :23679-23682

[2]

CHANG WC, 1993, J BIOL CHEM, V268, P18734

[3] Induction of 12-lipoxygenase expression by transforming growth factor-α in human epidermoid carcinoma A431 cells [J].

Chen, LC ;

Chen, BK ;

Liu, YW ;

Chang, WC .

FEBS LETTERS, 1999, 455 (1-2) :105-110

[4] The effect of foreign direct investment on firm growth: the case of Taiwan's manufacturers [J].

Chen, TJ ;

Ku, YH .

JAPAN AND THE WORLD ECONOMY, 2000, 12 (02) :153-172

[5]

CHEN YQ, 1994, CANCER RES, V54, P1574

[6] Lipoxygenase inhibitors abolish proliferation of human pancreatic cancer cells [J].

Ding, XZ ;

Iversen, P ;

Cluck, MW ;

Knezetic, JA ;

Adrian, TE .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1999, 261 (01) :218-223

[7] Lipoxygenase inhibition induced apoptosis, morphological changes, and carbonic anhydrase expression in human pancreatic cancer cells [J].

Ding, XZ ;

Kuszynski, CA ;

El-Metwally, TH ;

Adrian, TE .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1999, 266 (02) :392-399

[8] WAF1, A POTENTIAL MEDIATOR OF P53 TUMOR SUPPRESSION [J].

ELDEIRY, WS ;

TOKINO, T ;

VELCULESCU, VE ;

LEVY, DB ;

PARSONS, R ;

TRENT, JM ;

LIN, D ;

MERCER, WE ;

KINZLER, KW ;

VOGELSTEIN, B .

CELL, 1993, 75 (04) :817-825

[9] MOLECULAR-CLONING, PRIMARY STRUCTURE, AND EXPRESSION OF THE HUMAN PLATELET ERYTHROLEUKEMIA CELL 12-LIPOXYGENASE [J].

FUNK, CD ;

FURCI, L ;

FITZGERALD, GA .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (15) :5638-5642

[10]

Gewies A, 2000, CANCER RES, V60, P2163

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