Wang W, Higuchi C M
Prevention and Control Program, Cancer Research Center of Hawaii, University of Hawaii, Honolulu 96813, USA.
Cancer Lett. 1995 Nov 27;98(1):63-9.
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.
大量食用富含膳食抗氧化剂的水果和蔬菜与降低结直肠癌的发病率有关。膳食抗癌作用的一种潜在机制涉及诱导解毒的II期酶，包括NAD(P)H:醌还原酶（QR）和谷胱甘肽-S-转移酶（GST）。因此，本研究检测了膳食抗氧化剂维生素β-胡萝卜素、α-生育酚和抗坏血酸在人结肠癌细胞中诱导QR和GST活性细胞表达的能力。将Colo205细胞在存在或不存在各种浓度（10(-10)至10(-5)M）的每种抗氧化微量营养素的情况下培养，然后评估胞质QR和GST活性以及细胞生长。β-胡萝卜素、α-生育酚和抗坏血酸均导致QR活性呈剂量依赖性增加，且对细胞增殖无不良影响。为了研究β-胡萝卜素诱导QR的能力是否可归因于其转化为维生素A和/或其作为类胡萝卜素的抗氧化能力，对视黄醇、视黄酸和番茄红素诱导酶的能力进行了类似测试。尽管视黄醇和视黄酸在较高浓度（10(-6)至10(-5)M）时均具有抗增殖作用，但两种类视黄醇在生理浓度下均刺激QR。番茄红素是一种不能转化为维生素A的类胡萝卜素，没有生物活性。与对QR的影响相反，在这个体外模型中，GST活性不受任何测试微量营养素处理的影响。结果支持这样一种假设，即高膳食摄入维生素A、E和C可能通过诱导特定的解毒酶对结直肠癌提供部分保护。相对于QR诱导，β-胡萝卜素的抗氧化能力似乎比其作为无毒维生素A储存库的功能具有更小的生物学影响。测量结肠黏膜内的QR活性可能提供癌症易感性的指标，并且可能是涉及饮食调整或特定相关微量营养素的结直肠癌预防研究的合适替代终点生物标志物。
