title: Effect of cysteine proteinase inhibitors on murine B16 melanoma cell invasion in vitro.
abstract: Various types of proteinases are implicated in the malignant progression of human and animal tumors. Proteinase inhibitors may therefore be useful as therapeutic agents in anti-invasive and anti-metastatic treatment. The aims of this study were (1) to estimate the relative importance of proteinases in B16 cell invasion in vitro using synthetic, class-specific proteinase inhibitors and (2) to assess the inhibitory effect of some naturally occurring cysteine proteinase inhibitors. Serine proteinase inhibitor reduced invasiveness by up to 24%, whereas inhibition of aspartic proteinases reduced invasion by 11%. Synthetic inhibitors of cysteine proteinases markedly impaired invasion: cathepsin B inhibitors, particularly Ca-074Me, inhibited invasion from 20-40%, whereas cathepsin L inhibitor Clik 148 reduced invasion by 11%. The potato cysteine proteinase inhibitor PCPI 8.7 inhibited invasion by 21%, whereas another potato inhibitor, PCPI 6.6, and the mushroom cysteine proteinase inhibitor clitocypin had no effects. As the inhibitors that inhibited cathepsin B were in general more efficient at impairing the invasiveness, we conclude that of the two cysteine proteinases, cathepsin B plays a more important role than cathepsin L in murine melanoma cell invasion.
authors.affiliation: Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Ljubljana, Slovenia.
authors.forename: Natasa
authors.initials: N
authors.lastname: Sever
authors.forename: Metka
authors.initials: M
authors.lastname: Filipic
authors.forename: Joze
authors.initials: J
authors.lastname: Brzin
authors.forename: Tamara T
authors.initials: TT
authors.lastname: Lah
mesh_terms: D002401:Cathepsin B / Q000037:antagonists & inhibitors*; D056668:Cathepsin L; D002403:Cathepsins / Q000037:antagonists & inhibitors*; D003546:Cysteine Endopeptidases; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D005656:Fungal Proteins / Q000494:pharmacology; D007700:Kinetics; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D009361:Neoplasm Invasiveness; D011198:Solanum tuberosum / Q000201:enzymology; D014407:Tumor Cells, Cultured
chemical_list: C411656:Clitocypin protein, Clitocybe nebularis; D015853:Cysteine Proteinase Inhibitors; D005656:Fungal Proteins; D002403:Cathepsins; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; C534281:CTSL protein, human; D056668:Cathepsin L