Induction of NAD(P)H:quinone reductase by vitamins A, E and C in Colo205 colon cancer cells.
High consumption of fruits and vegetables which are abundant in dietary antioxidants has been linked to a reduced incidence of colorectal cancer. A potential mechanism of dietary anticarcinogenesis involves the induction of detoxifying phase II enzymes, including NAD(P)H:quinone reductase (QR) and glutathione-S-transferase (GST). This study therefore examined the ability of the dietary antioxidant vitamins beta-carotene, alpha-tocopherol and ascorbic acid to induce cellular expression of QR and GST activities in human colon cancer cells. Colo205 cells were cultured in the presence or absence of various concentrations (10(-10) to 10(-5) M) of each antioxidative micronutrient, then assessed for cytosolic QR and GST activities and cell growth. beta-Carotene, alpha-tocopherol and ascorbic acid each resulted in dose-dependent increases in QR activity, without adverse effects upon cell proliferation. To investigate whether the ability of beta-carotene to induce QR may be attributable to its conversion to vitamin A and/or to its antioxidant capacity as a carotenoid, retinol, retinoic acid, and lycopene were similarly tested for their capacity for enzyme induction. Although retinol and retinoic acid were both noted to be antiproliferative at higher concentrations (10(-6) to 10(-5) M), both retinoids stimulated QR at physiological concentrations. Lycopene, a carotenoid which is not converted to vitamin A, was devoid of biologic activity. By contrast with the effects upon QR, GST activity was unaffected by treatment with any of the micronutrients tested in this in vitro model. The results support a hypothesis that a high dietary consumption of vitamins A, E and C may confer partial protection against colorectal cancer by the induction of specific detoxifying enzymes. The antioxidant capacity of beta-carotene appears to have less biologic impact vis-a-vis QR induction than its function as a non-toxic reservoir of vitamin A. Measurements of QR activity within the colorectal mucosa may provide an index of cancer susceptibility, and may be an appropriate surrogate endpoint biomarker for colorectal cancer prevention studies involving diet modification or specific relevant micronutrients.
Prevention and Control Program, Cancer Research Center of Hawaii, University of Hawaii, Honolulu 96813, USA.
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D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D002338:Carotenoids / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000201:enzymology*; D004790:Enzyme Induction / Q000187:drug effects; D005982:Glutathione Transferase / Q000096:biosynthesis; D006801:Humans; D000077276:Lycopene; D018977:Micronutrients / Q000494:pharmacology; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured / Q000201:enzymology; D014801:Vitamin A / Q000494:pharmacology*; D014810:Vitamin E / Q000494:pharmacology*; D019207:beta Carotene
D000975:Antioxidants; D018977:Micronutrients; D019207:beta Carotene; D014801:Vitamin A; D014810:Vitamin E; D002338:Carotenoids; D016660:NAD(P)H Dehydrogenase (Quinone); D005982:Glutathione Transferase; D001205:Ascorbic Acid; D000077276:Lycopene