Expression of lipoxygenase in human bladder carcinoma and growth inhibition by its inhibitors.
OBJECTIVE
The metabolism of arachidonic acid by the cyclooxygenase or lipoxygenase pathway generates eicosanoids, which have been implicated in the pathogenesis of various human diseases, including cancer. They are now believed to have important roles in tumor promotion, progression and metastasis. The involvement of lipoxygenase expression and function in tumor growth and metastasis has been reported in human tumor cell lines.


METHODS
The expression of 5 and 12-lipoxygenase in patients with bladder tumor and chronic cystitis, and in normal bladder tissues was examined. We also examined the effects of their inhibitors on cell proliferation in a bladder cancer cell line. The expression of 5 and 12-lipoxygenase protein was detected by immunohistochemistry. The effects of lipoxygenase inhibitors on bladder cancer cell growth were examined by MTT (3-[4,5-dimethylthiazol-2-thiazolyl]-2,5-diphenyltetrazolium bromide) assay, while Hoechst (Sigma Chemical Co., St. Louis, Missouri) staining was used to determine whether lipoxygenase inhibitors induce apoptosis.


RESULTS
While slight 5 and 12-lipoxygenase expression was detected in chronic cystitis and normal bladder tissues, marked 5 and 12-lipoxygenase expression was detected in bladder cancer tissues. Lipoxygenase inhibitors caused marked inhibition of bladder cancer cells in a concentration and time dependent manner. Cells treated with lipoxygenase inhibitors showed chromatin condensation, cellular shrinkage, small membrane bound bodies (apoptotic bodies) and cytoplasmic condensation.


CONCLUSIONS
Lipoxygenase is induced in bladder cancer. Results suggest that lipoxygenase inhibitors may mediate potent antiproliferative effects against bladder cancer cells. Thus, lipoxygenase may become a new target in the treatment of bladder tumors.
Yoshimura
Rikio
R
Department of Urology, Osaka City University Medical School, 1-4-3 Asahi-machi, Abenoku, Osaka 545-8585, Japan. jasmin@med.osaka-cu.ac.jp
Matsuyama
Masahide
M
Tsuchida
Kenji
K
Kawahito
Yutaka
Y
Sano
Hajime
H
Nakatani
Tatsuya
T
D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001092:Arachidonate 12-Lipoxygenase / Q000235:genetics*; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D002295:Carcinoma, Transitional Cell / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D002908:Chronic Disease; D003556:Cystitis / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D005260:Female; D044950:Flavanones; D005419:Flavonoids / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007124:Immunoenzyme Techniques; D007211:Indoles / Q000494:pharmacology*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013722:Teprotide; D014407:Tumor Cells, Cultured / Q000473:pathology; D001743:Urinary Bladder / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D002722:Chlorobenzenes
D001092:Arachidonate 12-Lipoxygenase; D001094:Arachidonate 5-Lipoxygenase; D044950:Flavanones; D005419:Flavonoids; D007211:Indoles; D016859:Lipoxygenase Inhibitors; D013722:Teprotide; C060893:MK-886; D002722:Chlorobenzenes; C006680:baicalein