5-Lipoxygenase inhibitors attenuate growth of human renal cell carcinoma and induce apoptosis through arachidonic acid pathway.
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.
Matsuyama
Masahide
M
Department of Urology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
Yoshimura
Rikio
R
Mitsuhashi
Makoto
M
Tsuchida
Kenji
K
Takemoto
Yoshiaki
Y
Kawahito
Yutaka
Y
Sano
Hajime
H
Nakatani
Tatsuya
T
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
D005419:Flavonoids; D016859:Lipoxygenase Inhibitors; D012333:RNA, Messenger; D016718:Arachidonic Acid; C038044:baicalin; D009637:Masoprocol; D001092:Arachidonate 12-Lipoxygenase; D001094:Arachidonate 5-Lipoxygenase