CHEMOPREVENTIVE AGENTS - PROTEASE INHIBITORS

Certain protease inhibitors, called the anticarcinogenic protease inhi bitors in this review, are capable of preventing carcinogenesis in a w ide variety of in vivo and in vitro model systems. The anticarcinogeni c protease inhibitors are extremely potent agents with the ability to prevent cancer, with some unique characteristics as anticarcinogenic a gents. The anticarcinogenic protease inhibitors have the ability to ir reversibly suppress the carcinogenic process. They do not have to be c ontinuously present to suppress carcinogenesis. They can be effective when applied in both in vivo and in vitro carcinogenesis assay systems at long time periods after carcinogen exposure, and are effective as anticarcinogenic agents at extremely low molar concentrations. While s everal different types of protease inhibitors can prevent the carcinog enic process, the most potent of the anticarcinogenic protease inhibit ors on a molar basis are those with the ability to inhibit chymotrypsi n or chymotrypsin-like proteases. The soybean derived protease inhibit or, Bowman-Birk inhibitor (BBI), is a potent chymotrypsin inhibitor th at has been extensively studied for its ability to prevent carcinogene sis in many different model systems. Much of this review is focused on the characteristics of BBI as the anticarcinogenic protease inhibitor , as this is the protease inhibitor that has risen to the human trial stage as a human cancer chemopreventive agent. Part of this review hyp othesizes that the Bowman-Birk family of protease inhibitors plays a r ole in plants similar to that of cr, antichymotrypsin in people. Both BBI and alpha(1)-antichymotrypsin are potent inhibitors of chymotrypsi n and chymotrypsin-like enzymes, are highly anti inflammatory, and are thought to play important roles in the defense of their respective or ganisms. It is believed that BBI will be shown to play a major role in the prevention and/or treatment of several different diseases, in add ition to cancer. (C) 1998 Elsevier Science Inc.