Summary
Protease inhibitors and Vitamin E have been the most effective of the potential human cancer chemopreventive agents we have studied in the ability to suppress radiation-induced malignant transformation i in vitro. Although neither of these agents affect malignant cells, they appear to be working by different mechanisms to suppress the conversion of a cell to the malignant state, as their in vitro effects are markedly different. The effects of Vitamin E are reversible; if the compound is removed from cultures destined to produce transformed foci, transformed cells arise. The effects of protease inhibitors are irreversible in that these agents need to be present in cultures for only short periods of time to reverse the carcinogenic process (1). Protease inhibitors have their suppressive effect on carcinogenesis when present while cells are actively proliferating (1); vitamin E is effective when cells are in the confluent, stationary phase of growth (2). Relatively large concentrations of vitamin E (at nearly toxic levels) are necessary to inhibit transformation in vitro, while very low concentrations of protease inhibitor (nanomolar-picomolar ranges) are capable of suppressing the transformation process (1,2).
Protease inhibitors have proven to be so effective in our studies on the prevention of radiation transformation in vitro that we have now performed many other studies to determine the effects of these agents in animal model carcinogenesis systems. Studies with the soybean-derived Bowman-Birk inhibitor have shown that this protease inhibitor is capable of suppressing dimethylhydrazine-induced colon (3,4) and liver (4) carcinogenesis in mice, 7, 12 dimethylbenz(a)anthracene-induced oral carcinogenesis in hamsters (5) and 3-methylcholanthrene-induced lung tumorigenesis in mice (Witschi and Kennedy, unpublished data). Studies on the mechanism of the protease inhibitor suppression of carcinogenesis have suggested that these agents may act by suppressing oncogene expression or specific proteases involved in the conversion of a cell to the malignant state.
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References
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Kennedy, A.R. (1990). Effects of Protease Inhibitors and Vitamin E in the Prevention of Cancer. In: Prasad, K.N., Meyskens, F.L. (eds) Nutrients and Cancer Prevention. Experimental Biology and Medicine, vol 23. Humana Press. https://doi.org/10.1007/978-1-4612-4516-2_6
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DOI: https://doi.org/10.1007/978-1-4612-4516-2_6
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