Chemoprotection against cancer by phase 2 enzyme induction.
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, HgCl2 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.
Talalay
P
P
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Fahey
J W
JW
Holtzclaw
W D
WD
Prestera
T
T
Zhang
Y
Y
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects*; D005982:Glutathione Transferase / Q000096:biosynthesis; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000096:biosynthesis; D009369:Neoplasms / Q000517:prevention & control*; D010944:Plants / Q000737:chemistry; D051381:Rats
D016588:Anticarcinogenic Agents; D016660:NAD(P)H Dehydrogenase (Quinone); D005982:Glutathione Transferase