title: The effect of TNP-470 on cell proliferation and urokinase-type plasminogen activator and its inhibitor in human lung cancer cell lines.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Tsukuba Medical Center Hospital, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Ishikawa
authors.forename: H
authors.initials: H
authors.lastname: Satoh
authors.forename: H
authors.initials: H
authors.lastname: Kamma
authors.forename: T
authors.initials: T
authors.lastname: Naito
authors.forename: M
authors.initials: M
authors.lastname: Ohtsuka
authors.forename: T
authors.initials: T
authors.lastname: Ogata
authors.forename: S
authors.initials: S
authors.lastname: Hasegawa
mesh_terms: 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*
chemical_list: D000903:Antibiotics, Antineoplastic; D003510:Cyclohexanes; D017395:Plasminogen Activator Inhibitor 1; D012717:Sesquiterpenes; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator; D000077609:O-(Chloroacetylcarbamoyl)fumagillol