Bowman-Birk inhibitors, proteasome peptidase activities and colorectal pre neoplasias induced by 1,2-dimethylhydrazine in Swiss mice.
Bowman-Birk inhibitors (BBIs) are protein molecules containing two inhibitory domains for enzymes similar to trypsin and chymotrypsin. Interest in these inhibitors arose from their properties against the cancer chemically induced by 1,2-dimethylhydrazine (DMH). In this study the effect of two BBI preparations (from Glycine max and Macrotyloma axillare) were evaluated for the prevention of colorectal neoplasia induced by intraperitoneal injections of DMH, given at a dose of 30 mg/kg, during 12 weeks. Mice treated with DMH presented histopathological alterations consistent with tumor development, augmented CD44 expression and increased proteasome peptidase activities. Lysosomal fractions, obtained from the intestines, were chromatographed in a Sepharose-BBI column and increased activity for trypsin and chymotrypsin-like proteases recovered from DMH-treated animals. In parallel, mice treated for eight weeks with BBIs showed a decrease in the chymotrypsin and trypsin-like proteasome activities compared to animals fed on normal diet. For the groups receiving simultaneous treatment with DMH and BBIs, dysplasic lesions were not observed and proteasome peptidase activities were similar to the control group after the 24th week. These results suggest that the mechanism by which BBIs could prevent the appearance of pre neoplastic lesions is associated with inhibition of both the lysosomal and proteasome-dependent proteolytic pathways.
Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, Brazil. alessandrapcarli@hotmail.com
Alessandra
A
de Paula Carli
Paula Melo
PM
de Abreu Vieira
Karina Taciana Santos
KT
Silva
Renata Guerra
RG
de Sá Cota
Cláudia Martins
CM
Carneiro
William
W
Castro-Borges
Milton Hércules Guerra
MH
de Andrade
D019813:1,2-Dimethylhydrazine / Q000633:toxicity*; D000818:Animals; D015153:Blotting, Western; D002273:Carcinogens / Q000633:toxicity*; D002850:Chromatography, Gel; D015179:Colorectal Neoplasms / Q000139:chemically induced*; D018960:Hyaluronan Receptors / Q000378:metabolism; D008297:Male; D051379:Mice; D011230:Precancerous Conditions / Q000139:chemically induced*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D014358:Trypsin Inhibitor, Bowman-Birk Soybean / Q000494:pharmacology*
D002273:Carcinogens; C476399:Cd44 protein, mouse; D018960:Hyaluronan Receptors; D014358:Trypsin Inhibitor, Bowman-Birk Soybean; D046988:Proteasome Endopeptidase Complex; D019813:1,2-Dimethylhydrazine