Intestinal epithelial cells contain a high molecular weight protease subject to inhibition by anticarcinogenic protease inhibitors.
Protease inhibitors have been shown to be highly effective suppressors of carcinogenesis in both in vivo and in vitro model systems. For example, the soybean derived Bowman Birk inhibitor (BBI) has been shown to inhibit colon carcinogenesis. Although the precise mechanisms by which protease inhibitors suppress carcinogenesis are not known, it is believed that these compounds exert their anticarcinogenic effects by inhibiting specific cellular protease activities involved in the induction and/or expression of the transformed phenotype. In the current report, we describe a BBI-inhibitable proteolytic activity present in intestinal epithelial cells. The protease has a mass of approximately 125 kDa, cleaves gelatin and will bind to a BBI-affinity resin. Subcellular fractionation experiments indicate that this protease is located in the 10,000 x g pellet (lysosomal/golgi fraction) of IEC17 cell homogenates. Further studies have revealed that this proteolytic activity is inhibited by BBI and DFP, but unaffected by EDTA, indicating that this enzyme is a serine protease. Our results suggest that the 125-kDa protease is a 'target enzyme' of the BBI in these cells.
Habres
J M
JM
Department of Radiation Oncology, University of Pennsylvania, School of Medicine, Philadelphia 19104.
Billings
P C
PC
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002460:Cell Line; D002846:Chromatography, Affinity; D010450:Endopeptidases / Q000302:isolation & purification / Q000378:metabolism*; D004848:Epithelium / Q000201:enzymology; D007422:Intestines; D007700:Kinetics; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats
D000970:Antineoplastic Agents; D011480:Protease Inhibitors; D010450:Endopeptidases