The effect of TNP-470 on cell proliferation and urokinase-type plasminogen activator and its inhibitor in human lung cancer cell lines.
The plasminogen activator system has been found to modulate neoplastic spread and angiogenesis in tumors. An angiogenesis inhibitor, TNP-470, has been shown to possess potent antitumor activities in various types of cancer cells. We therefore investigated the inhibitory effect of TNP-470 on cancer cell proliferation, and the suppressive effect of TNP-470 on urokinase-type plasminogen activator (u-PA) and its inhibitor (PAI-1), in human lung cancer cell lines in vitro. TNP-470 inhibited cell proliferation in a dose-dependent manner in both cell lines. u-PA and PAI-1 in culture supernatants were suppressed with the concentrations of TNP-470, in association with a decrease in viable cancer cells. Unchanged serum levels of u-PA and PAI-1 would be of great advantage to the diseased patients, since the plasminogen activator system has a crucial function in the process of distant metastasis.
Ishikawa
H
H
Department of Internal Medicine, Tsukuba Medical Center Hospital, Japan.
Satoh
H
H
Kamma
H
H
Naito
T
T
Ohtsuka
M
M
Ogata
T
T
Hasegawa
S
S
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003510:Cyclohexanes; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis*; D010960:Plasminogen Activators / Q000096:biosynthesis*; D012717:Sesquiterpenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis*
D000903:Antibiotics, Antineoplastic; D003510:Cyclohexanes; D017395:Plasminogen Activator Inhibitor 1; D012717:Sesquiterpenes; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator; D000077609:O-(Chloroacetylcarbamoyl)fumagillol