title: Expression of 12-lipoxygenase in human renal cell carcinoma and growth prevention by its inhibitor.
abstract: The metabolism of arachidonic acid (AA) by either the cyclooxygenase (COX) or lipoxygenase (LOX) pathway generates eicosanoids, has been implicated in the pathogenesis of a variety of human diseases, including cancer, and may play important roles in tumor promotion, progression, and metastasis. The involvement of 12-LOX expression and function in tumor growth and metastasis has been reported in both murine and human tumor cell lines. The expression of 12-LOX in human renal cell carcinoma (RCC), normal kidney (NK) tissues and 3 kinds of RCC cell lines (Caki-1, A498, RC-1), and its effects on cell proliferation in 3 RCC cell lines were examined. Expression of 12-LOX protein was detected by immunohistochemistry and 12-LOX mRNA in RCC cell lines was detected by nested RT-PCR. Effects of 12-LOX inhibitor on RCC cell growth was examined by MTT assay, and to determine whether or not 12-LOX inhibitors induce apoptosis, we used Hoechst staining. While 12-LOX expression was detected slightly in NK tissues, a marked expression of 12-LOX was detected in RCC tissues. All human RCC cell lines expressed 12-LOX mRNA. The 12-LOX inhibitor baicalein caused marked inhibition of all three kinds of RCC cells in a concentration- and time-dependent manner. Cells treated with 12-LOX inhibitor showed chromatin condensation, cellular shrinkage, small membrane-bound bodies (apoptotic bodies), and cytoplasmic condensation. These results suggest 12-LOX may play a role in the progression of RCC in human tissue, and its inhibitors may become anticancer agents in human RCC.
authors.affiliation: Department of Urology, Osaka City Graduate School of Medicine, 1-4-3 Asahi-machi, Abenoku, Osaka 545-8585, Japan. jasmin@med.osaka-cu.ac.jp
authors.forename: Rikio
authors.initials: R
authors.lastname: Yoshimura
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Inoue
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kawahito
authors.forename: Makoto
authors.initials: M
authors.lastname: Mitsuhashi
authors.forename: Kenji
authors.initials: K
authors.lastname: Tsuchida
authors.forename: Masahide
authors.initials: M
authors.lastname: Matsuyama
authors.forename: Hajime
authors.initials: H
authors.lastname: Sano
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Nakatani
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001092:Arachidonate 12-Lipoxygenase / Q000096:biosynthesis / Q000235:genetics*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D044950:Flavanones; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D016859:Lipoxygenase Inhibitors; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D004791:Enzyme Inhibitors; D044950:Flavanones; D005419:Flavonoids; D016859:Lipoxygenase Inhibitors; C006680:baicalein; D001092:Arachidonate 12-Lipoxygenase