12-Lipoxygenase inhibition induced apoptosis in human gastric cancer cells.

Abstract

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.

• Authors: B C Wong, W P Wang, C H Cho, X M Fan, M C Lin, H F Kung, S K Lam
• Journal: Carcinogenesis (Carcinogenesis) Vol. 22 Issue 9 Pg. 1349-54 (Sep 2001) ISSN: 0143-3334 [Print] England
• PMID: 11532854 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Flavanones
• Flavonoids
• Growth Inhibitors
• Lipoxygenase Inhibitors
• RNA, Messenger
• baicalein
• 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
• Arachidonate 12-Lipoxygenase
• CASP3 protein, human
• CASP7 protein, human
• Caspase 3
• Caspase 7
• Caspases

Topics

• 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid (pharmacology)
• Apoptosis (drug effects, physiology)
• Arachidonate 12-Lipoxygenase (biosynthesis, genetics)
• Blood Platelets (enzymology)
• Blotting, Western
• Caspase 3
• Caspase 7
• Caspases (metabolism)
• Cell Division (drug effects, physiology)
• Drug Interactions
• Flavanones
• Flavonoids (pharmacology)
• Gene Expression Regulation, Neoplastic (drug effects)
• Growth Inhibitors (pharmacology)
• Humans
• Lipoxygenase Inhibitors (pharmacology)
• RNA, Messenger (biosynthesis, genetics)
• Stomach Neoplasms (enzymology, pathology)
• Tumor Cells, Cultured