Dietary ortho phenols that induce glutathione S-transferase and increase the resistance of cells to hydrogen peroxide are potential cancer chemopreventives that act by two mechanisms: the alleviation of oxidative stress and the detoxification of mutagenic xenobiotics.
Oxidative stress is implicated in the etiology of cancer, hence compounds that alleviate oxidative stress by inducing enzymes that defend against free radical damage might be useful as cancer chemopreventives. Glutathione S-transferase (GST) has been suggested to be a candidate for a critical enzyme in protecting cells against free radical damage, in part, because its level of induction correlates with protection of the cell line IMR-32 against hydrogen peroxide-induced oxidative stress. The present study identified dietary ortho phenols that both induce GST and protect the cell line IMR-32 against hydrogen peroxide-caused oxidative stress. The ortho phenol (o-phenol) inducers were better protectors against oxidative stress than a number of GST inducers that did not bear phenolic groups, possibly because the phenol residues of the ortho phenols allowed their action as antioxidants as well as inducers of GST. GST has previously been thought to protect cells against cancer by detoxifying mutagenic xenobiotics. The present results suggest that ortho phenol inducers of GST might be useful as cancer chemopreventives that act by two independent mechanisms, the alleviation of oxidative stress and the detoxification of mutagenic xenobiotics.
Fiander
H
H
Institute for Biological Sciences, National Research Council of Canada, K1A 0R6, Ottawa, Canada.
Schneider
H
H
D045784:Abietanes; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D004032:Diet; D004224:Diterpenes / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology; D044948:Flavonols; D005982:Glutathione Transferase / Q000096:biosynthesis* / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000633:toxicity*; D008658:Inactivation, Metabolic; D020128:Inhibitory Concentration 50; D007536:Isomerism; D009153:Mutagens / Q000493:pharmacokinetics* / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects*; D010616:Phenanthrenes / Q000494:pharmacology; D010636:Phenols / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D045784:Abietanes; D016588:Anticarcinogenic Agents; D000975:Antioxidants; D004224:Diterpenes; D005419:Flavonoids; D044948:Flavonols; D009153:Mutagens; D010616:Phenanthrenes; D010636:Phenols; D010936:Plant Extracts; C068623:carnosol; D006861:Hydrogen Peroxide; D005982:Glutathione Transferase; C018381:salvin; C017875:fisetin