Cancer prevention by protease inhibitors.
BACKGROUND
There is now compelling evidence that certain protease inhibitors have strong anticarcinogenic activity. A particular protease inhibitor derived from soybeans, the Bowman-Birk inhibitor, appears to be highly promising as a cancer chemopreventive agent. In this article, studies performed to characterize an extract of soybeans containing the Bowman-Birk inhibitor, termed Bowman-Birk inhibitor concentrate, are described.


METHODS
A number of different methods have been utilized to evaluate the efficacy and safety of Bowman-Birk inhibitor concentrate as a cancer chemopreventive agent in cells and animals. Bowman-Birk inhibitor concentrate has been studied extensively in animal carcinogenesis model systems and in vitro transformation systems.


RESULTS
Bowman-Birk inhibitor has been shown to prevent animal carcinogenesis in the absence of adverse side effects in several different systems. The dose proposed for human trials is approximately two orders of magnitude below doses shown to have no adverse effects in animal studies. At high doses, Bowman-Birk inhibitor concentrate has been shown to have a life-lengthening effect in mice. The intermediate marker endpoints known to be affected by Bowman-Birk inhibitor/Bowman-Birk inhibitor concentrate in in vitro and in vivo models systems include levels of oncogene expression and proteolytic activity. These intermediate marker endpoints, as well as histopathology, have been proposed for use in projected human trials which will be performed to evaluate Bowman-Birk inhibitor concentrate as an anticarcinogenic agent.


CONCLUSIONS
Bowman-Birk inhibitor concentrate is now ready for human trials and is likely to emerge as a powerful chemopreventive agent for human cancer.
Kennedy
A R
AR
Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia 19104.
D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use* / Q000633:toxicity; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D002986:Clinical Trials as Topic; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009369:Neoplasms / Q000517:prevention & control*; D009374:Neoplasms, Experimental / Q000517:prevention & control*; D011480:Protease Inhibitors / Q000627:therapeutic use* / Q000633:toxicity
D016588:Anticarcinogenic Agents; D011480:Protease Inhibitors