Effect of cysteine proteinase inhibitors on murine B16 melanoma cell invasion in vitro.
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.
Sever
Natasa
N
Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Ljubljana, Slovenia.
Filipic
Metka
M
Brzin
Joze
J
Lah
Tamara T
TT
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
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