QUERCETIN AND RUTIN AS INHIBITORS OF AZOXYMETHANOL-INDUCED COLONIC NEOPLASIA
QUERCETIN AND RUTIN AS INHIBITORS OF AZOXYMETHANOL-INDUCED COLONIC NEOPLASIA
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DOI：
10.1093/carcin/12.7.1193
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发表时间：
1991-07-01
期刊：
影响因子：
4.7
通讯作者：
NEWMARK, HL
中科院分区：
文献类型：
--
作者：
DESCHNER, EE;RUPERTO, J;NEWMARK, HL
研究人员给CF1雌性小鼠喂了50周的槲皮素（QU）和芦丁（RU）这两种常见于许多水果和蔬菜中的酚类黄酮，以评估这些化合物对偶氮甲醇（AOM）诱导的结肠肿瘤的抑制能力。除对照组饲喂AIN 76A饲粮外，另外5组饲喂在该饲粮中添加0.1、0.5或2.0% QU和1.0或4.0% RU的饲粮。急性研究显示，在生理盐水对照组中，接受任何剂量的QU或RU的组中结肠上皮细胞的任何增殖参数均未发生改变。然而，在aom处理的小鼠中，2% QU和4% RU均显著降低了过度增殖，并抑制了s期细胞向隐窝中部和上部的转移。此外，与对照组相比，饲喂这些浓度的QU和RU的小鼠aom诱导的发育不良病灶面积（FADs）显著减少（分别为0.2 +/- 0.4和0.4 +/- 0.5 vs 3.6 +/- 2.3）。无论治疗方法如何，肿瘤多发于结肠远端。与对照组相比，喂食2% QU的小鼠肿瘤发生率显著降低（25.0% vs 5.9%, P = 0.03）。喂食4% RU的小鼠只有抑制的趋势（25%对9.7%,P = 0.11）。然而，2% QU和4% RU均抑制了肿瘤的多样性，即与aom处理的对照小鼠相比，这些组中出现的肿瘤/动物数量更少（分别为1.2 vs 2.3, P = 0.005; 1.1 vs 2.3, P = 0.003）。显然，QU和RU在降低aom诱导的结肠上皮细胞过度增殖和FAD发生率方面表现出显著的活性。这种行为成功地预测了黄酮类化合物抑制肿瘤多样性和最终肿瘤发展的能力。
Dietary quercetin (QU) and rutin (RU), phenolic flavonoids commonly found in many fruits and vegetables, were provided to CF1 female mice for 50 weeks to assess the ability of these compounds to inhibit azoxymethanol (AOM)-induced colonic neoplasia. In addition to a control group fed an AIN 76A diet, five other groups received that diet to which was added either 0.1, 0.5 or 2.0% QU and 1.0 or 4.0% RU. Acute studies revealed that, among saline controls, no alteration of any proliferative parameters of colonic epithelial cells was observed among those groups receiving any dose of QU or RU. However, among the AOM-treated mice, both 2% QU and 4% RU significantly reduced hyperproliferation and inhibited the shift of S-phase cells to the middle and upper portion of crypts. Moreover, mice fed these concentrations of QU and RU had significantly fewer AOM-induced focal areas of dysplasia (FADs) than those fed the control diet (0.2 +/- 0.4 and 0.4 +/- 0.5 versus 3.6 +/- 2.3 respectively). Tumors occurred more frequently in the distal half of the colon, regardless of treatment. Compared with controls, mice fed 2% QU had a significantly reduced tumor incidence (25.0% versus 5.9%, P = 0.03). Those fed 4% RU showed only a trend toward inhibition (25% versus 9.7%, P = 0.11). Nevertheless, both 2% QU and 4% RU suppressed tumor multiplicity, i.e. fewer tumors/animal arose in these groups than in the AOM-treated control mice (1.2 versus 2.3, P = 0.005; 1.1 versus 2.3, P = 0.003 respectively). Clearly, QU and RU exhibit significant activity in reducing AOM-induced hyperproliferation of colonic epithelial cells and FAD incidence. This behavior successfully forecast the ability of both flavonoids to suppress tumor multiplicity and ultimately tumor development.