title: Antitumor activity of the type 1 plasminogen activator inhibitor and cytotoxic conjugate in vitro.
abstract: Many cancer cell lines and cancers overexpress receptor bound urokinase plasminogen activator on the cell surface. The urokinase plasminogen activator bound to its receptor remains on the cell surface for a prolonged period of time. When urokinase plasminogen activator/urokinase plasminogen activator receptor complex binds plasminogen activator inhibitor (PAI-1), the inhibitor triggers a series of events leading to internalization of the entire complex. This mechanism makes a very attractive target for localization and internalization of PAI-1-based cytotoxic compounds in cancer treatment. We investigated the antitumor activity of PAI-1/A-chain cholera toxin in vitro. Fibrosarcoma-derived HT1080 cells treated with PAI-1 conjugate showed at least 4 times higher cell killing than the control KD normal fibroblast cell line.
authors.affiliation: Chemistry Department, University of Toledo, Ohio 43606.
authors.forename: J
authors.initials: J
authors.lastname: Jankun
mesh_terms: D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000378:metabolism; D002772:Cholera Toxin / Q000494:pharmacology*; D003102:Colloids; D004355:Drug Stability; D005354:Fibrosarcoma / Q000737:chemistry / Q000188:drug therapy / Q000473:pathology; D006046:Gold; D006131:Growth Inhibitors / Q000494:pharmacology; D008856:Microscopy, Fluorescence; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000032:analysis; D055293:Receptors, Urokinase Plasminogen Activator; D012235:Rhodamines; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D001426:Bacterial Proteins; D003102:Colloids; D006131:Growth Inhibitors; D017395:Plasminogen Activator Inhibitor 1; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D012235:Rhodamines; D006046:Gold; D002772:Cholera Toxin