Chemoprotection against cancer by Phase 2 enzyme induction

• Published in: Toxicology Letters Vol. 82; pp. 173 - 179
• Main Authors: Talalay, Paul, Fahey, Jed W., Holtzclaw, W.David, Prestera, Tory, Zhang, Yuesheng
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Shannon Elsevier Ireland Ltd 01.12.1995; Amsterdam Elsevier Science
• Subjects: Animals; Anticarcinogenic Agents - pharmacology; Antioxidant response element (ARE); Biological and medical sciences; Carcinogenesis, carcinogens and anticarcinogens; Chemical agents; Electrophile response element (EpRE); Enzyme Induction - drug effects; Glutathione Transferase - biosynthesis; Glutathione transferases; Medical sciences; NAD(P)H Dehydrogenase (Quinone) - biosynthesis; Neoplasms - prevention & control; Plants - chemistry; Quinone reductase; Rats; Tumors; Vegetables; Antioxidant response element (ARE); Quinone reductase; Vegetables; Electrophile response element (EpRE); Glutathione transferases; Enzyme inducer; NAD-(P)-H dehydrogenase (quinone); Oxidative stress; Enzyme; Transferases; Malignant tumor; Anticarcinogen; Antioxidant; In vitro; Prevention; Carcinogen; Glutathione transferase; Plant origin; Oxidoreductases; Vegetable; Food; Glutathione
• ISSN: 0378-4274; 1879-3169
• DOI: 10.1016/0378-4274(95)03553-2

Mammalian cells have evolved elaborate mechanisms for protection against the toxic and neoplastic effects of electrophilic metabolites of carcinogens and reactive oxygen species. Phase 2 enzymes (e.g. glutathione transferase, NAD(P)H:quinone reductase, UDP-glucuronosyltransferases) and high intracellular levels of glutathione play a prominent role in providing such protection. Phase 2 enzymes are transcriptionally induced by low concentrations of a wide variety of chemical agents and such induction blocks chemical carcinogenesis. The inducers belong to many chemical classes including phenolic antioxidants, Michael reaction acceptors, isothiocyanates, 1,2-dithiole-3-thiones, trivalent arsenicals, HgCl 2 and organomercurials, hydroperoxides, and vicinal dimercaptans. Induction by all classes of inducers involves the antioxidant/electrophile response element (ARE/EpRE). Inducers are widely, but unequally, distributed among edible plants. Search for such inducer activity in broccoli led to the isolation of sulforaphane, an isothiocyanate that is a very potent Phase 2 enzyme inducer and blocks mammary tumor formation in rats.