12-Lipoxygenase inhibition induced apoptosis in human gastric cancer cells

• Published in: Carcinogenesis (New York) 2001-09, Vol.22 (9), p.1349-1354
• Main Authors: Wong, Benjamin Chun Yu, Wang, Wei Ping, Cho, Chi Hin, Fan, Xiao Ming, Lin, Marie Chia Mi, Kung, Hsiang Fu, Lam, Shiu Kum
• Format: Article
• Language: English
• Subjects: 12 hydroxyeicosatetraenoic acid; 12-HETE; 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid - pharmacology; 7-trihydroxyflavone; Antineoplastic agents; Apoptosis - drug effects; Apoptosis - physiology; Arachidonate 12-Lipoxygenase - biosynthesis; Arachidonate 12-Lipoxygenase - genetics; arachidonic acid; baicalein; Biological and medical sciences; Blood Platelets - enzymology; Blotting, Western; c-Jun NH2-terminal kinase; Caspase 3; Caspase 7; Caspases - metabolism; cdks; Cell Division - drug effects; Cell Division - physiology; Chemotherapy; COX; cyclin dependent kinases; cyclooxygenase; dimethyl sulfoxide; DMSO; Drug Interactions; EGF; epidermal growth factor; Flavanones; Flavonoids - pharmacology; Gene Expression Regulation, Neoplastic - drug effects; Growth Inhibitors - pharmacology; HPETE; Humans; hydroperoxyeicosatetraenoic acid; JNK; lipoxygenase; Lipoxygenase Inhibitors - pharmacology; LOX; MAPK; Medical sciences; mitogen activated protein kinase; Pharmacology. Drug treatments; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Stomach Neoplasms - enzymology; Stomach Neoplasms - pathology; TCA; trichloroacetic acid; Tumor Cells, Cultured
• ISSN: 0143-3334; 1460-2180; 1460-2180
• DOI: 10.1093/carcin/22.9.1349

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.