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In Vitro Studies of Anticarcinogenic Protease Inhibitors

  • Chapter
Protease Inhibitors as Cancer Chemopreventive Agents

Abstract

Several different types of agents have been shown to modify the yield of transformed cells in vitro. We have observed that certain protease inhibitors have the ability to suppress radiation- and chemical-induced malignant transformation in vitro in a highly significant fashion (Kennedy and Little, 1978, 1980a, 1981b; Littler al., 1979; Kennedy and Weichselbaum, 1981; Kennedy, 1982, 1984a, b, 1985a, 1988, 1990a; Yavelow etal., 1983, 1985; Baturay and Kennedy, 1986; Billings et al., 1987a, 1989). Several other investigators have also observed that some protease inhibitors can effectively suppress transformation in vitro (Kuroki and Drevon, 1979; Borek et al., 1979; DiPaolo et al., 1980; Popescu et al., 1980; Sun et al. 1988). The studies showing that protease inhibitors suppress transformation in vitro have utilized several different model systems, several different carcinogens (including x-radiation, UV light, chemical carcinogens, and steroid hormones as the inducing agents) and several different agents as promoters (or cocarcinogens) (reviewed in Kennedy, 1984a), as shown in Tables I and II (culture dishes containing transformed foci/cells are shown in Fig. 1). These results suggest that protease inhibitors are capable of suppressing similar processes induced by different carcinogens (with or without promotion or cocar-cinogenesis) in several different cell systems. Protease inhibitors have an unusual ability to suppress information in vitro in a highly significant manner, as opposed to the marginal effects observed for many other classes of possible human cancer chemopreventive agents which we have studied (Kennedy, 1984a,b, 1985b, 1986; Kennedy et al., 1984b). Not only are many other potential chemopreventive agents marginal in their effectiveness, but most of them need to be added to cultures at toxic or nearly toxic levels to observe any effect [e.g., see the effective levels of vitamin E (Radner and Kennedy, 1986)]. By comparison, protease inhibitors are effective at very low concentrations.

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Authors and Affiliations

  1. Department of Radiation Oncology, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA

    Ann R. Kennedy

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  1. Department of Environmental Medicine, New York University Medical Center, New York, New York, 10016, USA

    Walter Troll

  2. Department of Radiation Oncology, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA

    Ann R. Kennedy

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Kennedy, A.R. (1993). In Vitro Studies of Anticarcinogenic Protease Inhibitors. In: Troll, W., Kennedy, A.R. (eds) Protease Inhibitors as Cancer Chemopreventive Agents. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-2882-1_3

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