PROTEASE INHIBITORS AND CARCINOGENESIS - A REVIEW

The brief review article deals with the subject of anticarcinogenic ac tivity of protease inhibitors (PI). Three basic premises are made: (1) Although PI are prevalent constituents of dietary staples such as soy products, which have been epidemiologically associated with reduced c ancer incidences at multiple target sites, they are unlikely to be the active anticarcinogenic entities. Cooked soy products, which are devo id of PI activity, are equally as effective at reducing cancer develop ment as raw soy products. Isoflavones are likely to represent major ch emopreventive agents in soy, although other constituents may well cont ribute. (2) Although supplementation of diets with PI (natural or synt hetic), or direct topical administration, results in lower cancer inci dences in many experimental models in vivo, this effect appears to be indirect. Dietary PI are, in general, poorly absorbed from the GI trac t, and never reach target organs in any measurable quantity. The most attractive hypothesis is that dietary PI could induce synthesis and di stribution of endogenous PI (acute-phase reactants), which have widesp read effects on cell growth and behavior. Effects of topical administr ation of PI also encompass prominent anti-inflammatory effects. (3) A spectrum of PI inhibit in vitro transformation induced by a variety of carcinogenic agents. Their effects can be grouped into three basic ca tegories, affecting: (a) signal transduction pathways; (b) DNA repair processes; and (c) nuclear proteases. I suggest that the nuclear multi catalytic protease activity, in particular the chymotrypsin-like activ ity, represents an important cellular target for which considerable an ecdotal support can be garnered.