Activity and inhibition by cytotoxic and antimetastatic drugs of cathepsin B-like cysteine proteinase in transplantable leukemias in mice.
The cellular levels of cathepsin B-like cysteine proteinases have been determined in a panel of transplantable mouse leukemias possessing a different potential to metastatize to the liver after i.p. implantation. The higher enzymatic activity observed in L1210 leukemic cells matches their higher capacity for hepatic infiltration. No significant difference is observed for TLX5 lymphoma and P388 leukemia, in spite of their different liver invasiveness, and their enzymatic levels do not significantly differ from that of the non-invasive Ehrlich ascitic carcinoma. The in vivo administration of the antimetastatic drugs ICRF159 and DM-COOK, or of the cytotoxic drugs cyclophosphamide, cisplatin, CCNU and GANU, does not cause a pattern of enzyme inhibition matching the tumor metastatic potential and the increase in life-span of the treated tumor bearing mice, indicating that the inhibition of cathepsin B-like cysteine proteinase is not involved in either their cytotoxic or their antimetastatic action.
Giraldi
T
T
Sava
G
G
Zorzet
S
S
Perissin
L
L
Piccini
P
P
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002401:Cathepsin B / Q000032:analysis* / Q000037:antagonists & inhibitors; D003546:Cysteine Endopeptidases; D010450:Endopeptidases / Q000032:analysis*; D005260:Female; D007942:Leukemia, Experimental / Q000188:drug therapy / Q000201:enzymology*; D008223:Lymphoma / Q000188:drug therapy / Q000201:enzymology; D051379:Mice; D008815:Mice, Inbred Strains; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D011480:Protease Inhibitors; D011929:Razoxane / Q000494:pharmacology; D014226:Triazenes / Q000494:pharmacology
D000970:Antineoplastic Agents; D011480:Protease Inhibitors; D014226:Triazenes; D011929:Razoxane; C030838:1-(4-carboxyphenyl)-3,3-dimethyltriazene; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D002401:Cathepsin B