Inhibition of neoplastic transformation and bioavailability of dietary flavonoid agents.

Inhibition of neoplastic transformation and bioavailability of dietary flavonoid agents.
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抑制肿瘤转化和膳食黄酮类药物的生物利用度。

DOI:
10.1007/978-1-4615-5335-9_17
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发表时间:
1998
影响因子:
--
通讯作者:
Yuichiro Tanaka
Yuichiro Tanaka
中科院分区:
医学4区
文献类型:
--
作者:
A. Franke;R. Cooney;L. Custer;L. Mordan;Yuichiro Tanaka

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评估化学品(包括食用植物产品)的未知生物效应需要评估生物活性和生物利用度。流行病学研究一致表明,食用水果和蔬菜具有预防癌症的作用,但人们对哪种植物化学物质解释了这一观察结果知之甚少。与食物类别本身相比,通常研究的抗氧化微量营养素与癌症预防的相关性不太一致,这表明其他植物化学物质或食品组合在预防癌症方面发挥着关键作用。我们研究了主要膳食类黄酮和异黄酮类化合物在抑制 C3H 10T1/2 小鼠成纤维细胞中 3-甲基胆蒽诱导的肿瘤转化方面的作用。我们发现,大多数测试的酚类药物的有效性等于或优于已知的化学预防剂,例如类胡萝卜素或维生素。橙皮素、橙皮苷和儿茶素是测试的黄酮类化合物中最有效的药物,在接触致癌物质后以 1.0 µM 浓度施用时,可完全抑制转化。结构活性比较表明,在测试的化合物中,环“B”中具有邻位联苯酚结构和饱和“C”环的黄酮类化合物表现出最强的效果。大多数测试的药物都表现出剂量依赖性模式。有趣的是,除非组合使用,否则大豆异黄酮类化合物的活性较弱,这表明存在协同效应。此外,还开发了 HPLC 技术来测定人体生物体液(包括尿液、血浆和母乳)中异黄酮类化合物的生物利用度。我们观察到异黄酮类化合物的吸收、分布和消除相对较快,包括可能由于肠肝循环而产生的双相模式。尿液、血浆和母乳中异黄酮的总峰值水平分别为 60 µM、2 µM 和 0.2 µM,并且在食用大豆食品后 8-12 小时达到。研究发现,在人体体液中检测到的水平对抑制肿瘤转化具有高度活性,特别是考虑到大豆食品中主要异黄酮类化合物大豆黄酮和金雀异黄酮组合观察到的协同效应。
Evaluation of unknown biological effects of chemicals including food plant products requires the assessment of bioactivity and bioavailability. Epidemiologic studies show consistently a cancer protective effect of fruit and vegetable consumption, but there is little understanding of which phytochemicals account for this observation. Commonly studied antioxidant micronutrients are less consistently correlated with cancer protection relative to the food groups themselves, suggesting that other phytochemicals or a combination of food products play key roles in preventing cancer. We investigated the effects of the predominant dietary flavonoids and isoflavonoids at inhibiting neoplastic transformation induced by 3-methylcholanthrene in C3H 10T1/2 murine fibroblasts. We found that most phenolic agents tested were equal to or superior to known chemopreventive agents such as carotenoids or vitamins in effectiveness. Hesperetin, hesperidin and catechin were the most potent agents among the flavonoids tested, inhibiting transformation completely when applied at 1.0 microM after exposure to the carcinogen. Structure-activity comparison revealed that among the compounds tested, flavonoids with a vicinal diphenol structure in ring 'B' and a saturated 'C' ring exhibited the strongest effects. Most agents tested showed dose-dependent patterns. Interestingly, the soy isoflavonoids were weakly active except when applied in combination, suggesting a synergistic effect. In addition, HPLC techniques were developed for determining the bioavailability of isoflavonoids in human biological fluids including urine, plasma and breast milk. We observed a relatively fast absorption, distribution and elimination of isoflavonoids including a biphasic pattern probably due to enterohepatic circulation. Total peak isoflavone levels in urine, plasma and in breast milk were found to be 60 microM, 2 microM and 0.2 microM, respectively and were reached 8-12 hours after consumption of soy foods. Levels detected in human body fluids were found to be highly active at inhibiting neoplastic transformation, especially considering synergistic effects observed for combinations of daidzein and genistein, the predominant isoflavonoids occurring in soy foods.
DOI: 10.1016/s0002-8223(95)00214-6
发表时间: 1995-07-01
影响因子: --
作者:
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影响因子: 4.2
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DOI: --
发表时间: 1995
期刊: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子: --
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发表时间: 1993-03-01
影响因子: 11.1
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DOI: --
发表时间: 1995-06
期刊: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子: --
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Mao-jung Lee;Zhi-Yuan Wang;He Li;Laishun Chen;Yang Sun;Steve Gobbo;D. Balentine;Chung S. Yane
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