Antitumor effects of lipoxygenase inhibitors on murine bladder cancer cell line (MBT-2).
Arachidonic acid (AA) metabolites derived from both the lipoxygenase (LOX) and cyclooxygenase (COX) pathways transduce a variety of signals related to cell growth. Selective blockade of the different metabolic pathways of AA (using a general LOX inhibitor NDGA, a 5-LOX inhibitor AA861, a 12-LOX inhibitor baicalein and a general COX inhibitor ibuprofen) revealed that murine bladder cancer cell line (MBT-2) cell proliferation was inhibited by the LOX inhibitors concentration-dependently, but not by the COX inhibitor. Among the LOX inhibitors, baicalein showed the strongest inhibition and induced apoptosis of MBT-2. Proliferation of MBT-2 was also significantly inhibited by 12-LOX antisense oligonucleotides. In an in vivo experiment, the antitumor effects of baicalein administration on C3H/HeN mice implanted with MBT-2 were recognized. These results suggested that LOX inhibition may be significant in the treatment of bladder cancer.
Ikemoto
Shinichi
S
Department of Urology, Osaka City University Graduate School of Medicine, Osaka, Japan.
Sugimura
Kazunobu
K
Kuratukuri
Katuyuki
K
Nakatani
Tatuya
T
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001092:Arachidonate 12-Lipoxygenase / Q000235:genetics; D045744:Cell Line, Tumor; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D044950:Flavanones; D005419:Flavonoids / Q000494:pharmacology; D008084:Lipoxygenase / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000201:enzymology*
D000970:Antineoplastic Agents; D016861:Cyclooxygenase Inhibitors; D044950:Flavanones; D005419:Flavonoids; D016859:Lipoxygenase Inhibitors; D016376:Oligonucleotides, Antisense; C006680:baicalein; D008084:Lipoxygenase; D001092:Arachidonate 12-Lipoxygenase