Cathepsin B in the growth of colorectal cancer: suppressive effect of leupeptin on the growth of DMH-induced rat colon neoplasm.
Cathepsin B, a thiol protease, has been reported to be involved in cancer progression and metastasis. The suppressive effects of two kinds of protease inhibitors, leupeptin and dietary camostate (FOY-305), on tumorigenesis and progression in 1, 2-dimethylhydrazine (DMH)-induced rat colon neoplasm were examined in relation to tissue cathepsin B activity. Male Donryu rats were treated with leupeptin or FOY-305 during or after the administration of DMH. There were no significant differences in average tumor numbers among all DMH-treated groups. However, the percentage of small tumors was significantly higher in the group in which leupeptin was supplied during DMH administration. This trend was not recognized in the FOY-305-treated groups. The ratio of cathepsin B activity in the tumors to that in the tumor-bearing tissue (T/Tb) was significantly increased with increasing tumor size (P = 0.009). The cathepsin B activity levels in the tumor-bearing mucosa in the groups which received leupeptin or FOY-305 following DMH treatment were both significantly lower than that in the group which received neither protease inhibitor (P = 0.046 and P = 0.0067, respectively). The results obtained indicate that leupeptin may have suppressed tumor growth by lowering the tissue cathepsin B activity.
Satoh
Y
Y
First Department of Internal Medicine, Okayama University Medical School, Japan.
Higashi
T
T
Nouso
K
K
Shiota
T
T
Kinugasa
N
N
Yoshida
K
K
Uematsu
S
S
Nakatsukasa
H
H
Nishimura
Y
Y
Tsuji
T
T
D019813:1,2-Dimethylhydrazine; D000818:Animals; D002273:Carcinogens; D002401:Cathepsin B / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology*; D004127:Dimethylhydrazines; D004952:Esters; D016670:Gabexate / Q000031:analogs & derivatives*; D006146:Guanidines / Q000494:pharmacology*; D007976:Leupeptins / Q000494:pharmacology*; D008297:Male; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats
D002273:Carcinogens; D004127:Dimethylhydrazines; D004952:Esters; D006146:Guanidines; D007976:Leupeptins; D011480:Protease Inhibitors; C034532:camostat; D016670:Gabexate; D002401:Cathepsin B; D019813:1,2-Dimethylhydrazine; C032854:leupeptin