Expression of lipoxygenase in human prostate cancer and growth reduction by its inhibitors.
The metabolism of arachidonic acid by either the cyclooxygenase (COX) or lipoxygenase (LOX) pathway generates eicosanoids, which have been implicated in the pathogenesis of a variety of human diseases, including cancer. They are believed to play important roles in tumor promotion, progression, and metastasis. Involvement of LOXs expression and function in tumor growth and metastasis has been reported in human tumor cell lines. Expressions of 5- and 12-LOX in prostate cancer (PC) patients, prostatic intraepithelial neoplasia (PIN), benign prostatic hyperplasia (BPH), and normal prostate (NP) tissues were examined, as well as effects of their inhibitors on cell proliferation in 2 PC cell lines (PC3, DU-145). Expression of 5- and 12-LOX protein was detected by immunohistochemistry. Effects of LOX inhibitors on prostate cancer 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 expressions were slightly detected in BPH and NP tissues, marked expressions of 5- and 12-lipoxygenase were detected in PIN and PC tissues. The LOX inhibitors caused marked reduction of prostate cancer cells in a concentration- and time-dependent manner. The LOX inhibitors caused marked inhibition of PC cells through apoptosis. LOX is induced in prostate cancer, and our results suggest that LOX inhibitors may mediate potent antiproliferative effects against prostate cancer cells. Thus, LOX may become a new target in treatment of prostate cancer.
Matsuyama
Masahide
M
Department of Urology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan.
Yoshimura
Rikio
R
Mitsuhashi
Makoto
M
Hase
Taro
T
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*; D016022:Case-Control Studies; D002455:Cell Division / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D011470:Prostatic Hyperplasia / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D019048:Prostatic Intraepithelial Neoplasia / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics; D014407:Tumor Cells, Cultured
D016859:Lipoxygenase Inhibitors; D001092:Arachidonate 12-Lipoxygenase; D001094:Arachidonate 5-Lipoxygenase