title: 5-Lipoxygenase inhibitors attenuate growth of human renal cell carcinoma and induce apoptosis through arachidonic acid pathway.
abstract: The metabolism of arachidonic acid by either the cyclooxygenase or lipoxygenase (LOX) pathway is believed to play an important role in tumor promotion. We investigated the expression of 5- and 12-LOX in renal cell carcinoma (RCC), as well as the effects of their inhibitors on cell proliferation in 2 RCC cell lines (Caki-1 and A498). Expression of 5- and 12-LOX was detected by immunohistochemistry and RT-PCR. Effects of LOX inhibitors on RCC cell growth were examined by MTT assay, and Hoechst staining was used to determine whether or not the LOX inhibitors induce apoptosis. While 5- and 12-LOX expression levels were slightly detected in NK tissues, marked expressions of 5- and 12-LOX were detected in RCC tissues. 5-LOX inhibitors caused marked reduction of RCC cells in a concentration- and time-dependent manner. The effect of the 5-LOX inhibitor was stronger than the 12-LOX inhibitor. Furthermore, the 5-LOX inhibitor caused a marked reduction of RCC cells through apoptosis. LOX, especially 5-LOX, is induced in RCC, and the results suggest that the 5-LOX inhibitor may mediate potent anti-proliferative effects against RCC cells. Thus, 5-LOX may become a new target in treatment of RCC.
authors.affiliation: Department of Urology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
authors.forename: Masahide
authors.initials: M
authors.lastname: Matsuyama
authors.forename: Rikio
authors.initials: R
authors.lastname: Yoshimura
authors.forename: Makoto
authors.initials: M
authors.lastname: Mitsuhashi
authors.forename: Kenji
authors.initials: K
authors.lastname: Tsuchida
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Takemoto
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kawahito
authors.forename: Hajime
authors.initials: H
authors.lastname: Sano
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Nakatani
mesh_terms: D000368:Aged; D017209:Apoptosis / Q000187:drug effects*; D001092:Arachidonate 12-Lipoxygenase / Q000235:genetics / Q000378:metabolism; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D008297:Male; D009637:Masoprocol / Q000494:pharmacology; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013997:Time Factors
chemical_list: D005419:Flavonoids; D016859:Lipoxygenase Inhibitors; D012333:RNA, Messenger; D016718:Arachidonic Acid; C038044:baicalin; D009637:Masoprocol; D001092:Arachidonate 12-Lipoxygenase; D001094:Arachidonate 5-Lipoxygenase