Mechanism of Anticarcinigenic Effects of Myristicin

University Of Texas-Pan American, Edinburg TX

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Abstract

DESCRIPTION (provided by applicant): A compelling body of evidence accumulated through epidemiologic studies and experimental investigations strongly suggest that consumption of vegetables and fruits provide protection against cancer presumably by induction of enzymes that are involved in carcinogenic metabolism. Although the mechanism is not entirely understood, enhancement of detoxification of carcinogenic electrophiles by inducing Phase-II detoxification enzymes such as glutathione S-transferase (GST) and NAD(P)H: quinone reductase (QR) appears to be the single most important component of the mechanisms. GSTs are known to metabolize a number of carcinogens thus minimizing the risk of DNA damage. Through redox cycling, QR mediates the two-electron reduction of quinones leading to the formation of relatively stable hydroquinones, thereby protecting against quinonide-mediated carcinogenesis. A positive correlation between the anticarcinogens, and their ability to induce GST and QR activities, has been observed; more recently an association between decreased GST activity and increased risk of certain cancers has been established. These studies have inspired the search of naturally occurring phytochemicals capable of inducing detoxification enzymes. Our studies and others show that Myristicin, an active constituent of parsley and other plants and vegetables, induces GST activity and inhibits tumorigenesis in mouse tissues and thus appears to be a potential chemoprotective agent. Since induction of GSTs, like their distribution, is not uniform among tissues of different gender and strains, and that specific GSTs are known to exhibit preferential metabolic activity towards carcinogens, the functional characteristics of myristicin induced GSTs isoenzymes from tissues of animals will be determined against carcinogenic substrates. The chemopreventive efficacy of myristicin will be established using in vivo and in vitro models. The results are expected to help us understand the Phase-II enzyme induction by myristicin and its potential in developing pharmacologically effective dietary strategies for cancer chemoprevention.