Enzyme inhibitors in relation to cancer therapy

In the last 11 years the authors have succeeded in isolating nearly 40 enzyme inhibitors of small molecular size from microbial origins. These inhibitors proved to be not only useful tools in analyses of homeostasis of living organisms but also promising agents for cancer chemotherapy. Leupeptin was originally isolated as an inhibitor against serine or thiol proteases such as trypsin, plasmin, papain and cathepsin B. And soon it was demonstrated that leupeptin suppressed chemical carcinogenesis in rats. Pepstatin has an extremely strong activity to inhibit pepsin and cathepsin D. It also inhibits ascites accumulation caused by neoplastic diseases. Bestatin is a specific inhibitor against aminopeptidase B and leucine aminopeptidase. The enzymes are located on the surface membrane in various kinds of cells including lymphocytes. Bestatin was shown to enhance not only blastogenesis of lymphocytes in vitro but also establishment of delayed-type hypersensitivity in vivo. Combined use of bestatin and other antitumor agents gave promising results in animal experiments. Studies on enzyme inhibitors have provided us a new approach to cancer chemotherapy.