12-Lipoxygenase inhibition induced apoptosis in human gastric cancer cells
2001; Oxford University Press; Volume: 22; Issue: 9 Linguagem: Inglês
10.1093/carcin/22.9.1349
ISSN1460-2180
AutoresBenjamin Chun Yu Wong, Wei Ping Wang, Chi Hin Cho, Xiao Fan, Marie Chia Mi Lin, Hsiang Fu Kung, Shiu Kum Lam,
Tópico(s)Inflammatory mediators and NSAID effects
ResumoArachidonic 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.
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