Anticarcinogenic Actions of Protease Inhibitors

Abstract

There is a great variation in cancer incidence with diet, as has been recently reviewed (1,2). Epidemiological data suggest that environmental, specifically nutritional, factors play a major role in the etiology of cancer at many different sites (1–3). There are now several epidemiologic studies which suggest that components of vegetables might play a beneficial role in lowering the incidence of cancer (some examples of such studies are given in references 1-4). Although many compounds with anticarcinogenic potential are present in vegetables, it is possible that anticarcinogenic protease inhibitors contribute to the low cancer rates observed in certain human populations with high levels of vegetables in the diet. For example, the low cancer incidence rates in the Japanese and Seventh-Day adventists could be due to high levels of dietary protease inhibitors; it has been estimated that individuals in these populations ingest, on the average, more than 330 mg of protease inhibitors per day (3). There are, however, many other hypotheses which have been presented to explain the low cancer rates in these human populations. So many different variables are present in the diet that the effect of any specific anticarcinogenic agent cannot be distinguished in such epidemiologic studies; however, it is possible to distinguish the effects of specific anticarcinogenic agents in laboratory experiments. In this report, our own laboratory studies on anticarcinogenic protease inhibitors will be summarized and discussed. Although laboratory studies can give much information about the effects of potential chemopreventive agents, ultimately epidemiologic intervention studies must be performed to determine whether candidate chemopreventive agents are truly capable of preventing cancer in human populations. The current evidence that dietary protease inhibitors do have a role in lowering the cancer incidence in human populations has recently been reviewed (6 and 7).