Journal Article

12-Lipoxygenase inhibition induced apoptosis in human gastric cancer cells

Benjamin Chun Yu Wong, Wei Ping Wang, Chi Hin Cho, Xiao Ming Fan, Marie Chia Mi Lin, Hsiang Fu Kung and Shiu Kum Lam

in Carcinogenesis

Volume 22, issue 9, pages 1349-1354
Published in print September 2001 | ISSN: 0143-3334
Published online September 2001 | e-ISSN: 1460-2180 | DOI:
12-Lipoxygenase inhibition induced apoptosis in human gastric cancer cells

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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.

Keywords: AA, arachidonic acid; baicalein, 5,6,7-trihydroxyflavone; cdks, cyclin dependent kinases; COX, cyclooxygenase; DMSO, dimethyl sulfoxide; EGF, epidermal growth factor; 12-HETE, 12 hydroxyeicosatetraenoic acid; HPETE, hydroperoxyeicosatetraenoic acid; JNK, c-Jun NH2-terminal kinase; LOX, lipoxygenase; MAPK, mitogen activated protein kinase; TCA, trichloroacetic acid.

Journal Article.  4341 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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