title: Inhibition of 5-lipoxygenase triggers apoptosis in pancreatic cancer cells.
abstract: The 5-lipoxygenase (5-LOX) pathway has been associated with a variety of inflammatory diseases including asthma, atherosclerosis, rheumatoid arthritis, cancer and liver fibrosis. Several classes of 5-LOX inhibitors have been identified, but only one drug, zileuton, a redox inhibitor of 5-LOX, has been approved for clinical use. In the present study, 5-LOX was found to be overexpressed not only in pancreatic cancer cell lines but also in tissue samples of patients suffering from pancreatic adenocarcinoma. There was a close correlation between the tumor expression levels of 5-LOX mRNA and protein and the clinicopathological patient characteristics including lymph node metastasis and TNM stage. Zileuton suppressed the proliferation of SW1990 cells in a concentration- and time‑dependent manner. In addition, zileuton induced SW1990 cells to undergo apoptosis and significantly decreased 5-LOX expression. The number of apoptotic cells, estimated by flow cytometry, Annexin V/PI assay, TUNEL staining and sub‑diploid population was significantly higher than that of the control. These results suggest that the level of 5-LOX expression was increased in pancreatic cancer tissues and may be related to lymph node metastasis and TNM stage.
authors.affiliation: Department of Gastroenterology, Affliliated Hospital of Nantong University, Jiangsu, Nantong 226001, P.R. China.
authors.forename: Guo-Xiong
authors.initials: GX
authors.lastname: Zhou
authors.affiliation: Department of Gastroenterology, Affliliated Hospital of Nantong University, Jiangsu, Nantong 226001, P.R. China.
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Ding
authors.affiliation: Department of Gastroenterology, Affliliated Hospital of Nantong University, Jiangsu, Nantong 226001, P.R. China.
authors.forename: Sheng-Bao
authors.initials: SB
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology, Affliliated Hospital of Nantong University, Jiangsu, Nantong 226001, P.R. China.
authors.forename: Hai-Feng
authors.initials: HF
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Affliliated Hospital of Nantong University, Jiangsu, Nantong 226001, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cao
authors.affiliation: Department of Gastroenterology, Affliliated Hospital of Nantong University, Jiangsu, Nantong 226001, P.R. China.
authors.forename: Li-Shuai
authors.initials: LS
authors.lastname: Qu
authors.affiliation: Department of Gastroenterology, Affliliated Hospital of Nantong University, Jiangsu, Nantong 226001, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D000368:Aged; D017209:Apoptosis; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D006918:Hydroxyurea / Q000031:analogs & derivatives* / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
chemical_list: D016859:Lipoxygenase Inhibitors; D001094:Arachidonate 5-Lipoxygenase; C583212:ALOX5 protein, human; C063449:zileuton; D006918:Hydroxyurea