Suppression of colon carcinogenesis by bioactive compounds in grapefruit.
Suppression of colon carcinogenesis by bioactive compounds in grapefruit.
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DOI：
10.1093/carcin/bgi318
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发表时间：
2006-06
期刊：
影响因子：
4.7
通讯作者：
J. Vanamala;Tety Leonardi;B. Patil;S. Taddeo;M. Murphy;L. Pike;R. Chapkin;J. Lupton;N. Turner
中科院分区：
文献类型：
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作者：
J. Vanamala;Tety Leonardi;B. Patil;S. Taddeo;M. Murphy;L. Pike;R. Chapkin;J. Lupton;N. Turner
本研究评估的假设，即未经处理和辐照葡萄柚以及分离的柑橘类化合物柚苷和柠檬苦素将保护对氧化偶氮甲烷（AOM）诱导的异常隐窝灶（ACF）通过抑制增殖和提高细胞凋亡，通过抗炎活性。雄性Sprague-Dawley大鼠（n = 100）被提供五种饮食中的一种：对照（未添加葡萄柚组分）、未处理或辐照（300戈伊，137 Cs）的葡萄柚果肉粉（13.7 g/kg）、柚苷（200 mg/kg）或柠檬苦素（200 mg/kg）。在第3和4周期间向大鼠注射生理盐水或AOM（15 mg/kg），并切除结肠（第二次注射后6周）以评价ACF、增殖、凋亡和环氧合酶（考克斯）-2和诱导型一氧化氮合酶（iNOS）蛋白水平。实验饮食对盐水注射大鼠中测量的变量没有影响。但在AOM注射大鼠中，与对照组相比，实验饮食抑制了（P <或= 0.02）异常隐窝和高多样性ACF（HMACF; P <或= 0.01）的形成和增殖指数（P <或= 0.02）。只有未经处理的葡萄柚和柠檬苦素抑制了（P <或= 0.04）HMACF/cm和增殖区的扩张（P <或= 0.008），这发生在摄入对照饮食的AOM注射大鼠中。与对照饮食相比，所有饮食均提高了AOM注射大鼠的凋亡指数（P <或= 0.05）;然而，未处理的葡萄柚和柠檬苦素的增强作用最大。未处理的葡萄柚和柠檬苦素饮食抑制了在食用对照饮食的AOM注射大鼠中观察到的iNOS（P <或= 0.003）和考克斯-2（P <或= 0.032）水平的升高。虽然辐照葡萄柚和柚皮苷抑制AOM注射大鼠的iNOS水平，但没有观察到对考克斯-2水平的影响。因此，较低水平的iNOS和考克斯-2与增殖的抑制和凋亡的上调相关，这可能导致了未处理的葡萄柚和柠檬苦素提供的大鼠中HMACF数量的减少。这些结果表明，食用葡萄柚或柠檬苦素可能有助于抑制结肠癌的发展。
This study evaluated the hypothesis that untreated and irradiated grapefruit as well as the isolated citrus compounds naringin and limonin would protect against azoxymethane (AOM)-induced aberrant crypt foci (ACF) by suppressing proliferation and elevating apoptosis through anti-inflammatory activities. Male Sprague-Dawley rats (n = 100) were provided one of five diets: control (without added grapefruit components), untreated or irradiated (300 Gy, 137Cs) grapefruit pulp powder (13.7 g/kg), naringin (200 mg/kg) or limonin (200 mg/kg). Rats were injected with saline or AOM (15 mg/kg) during the third and fourth week and colons were resected (6 weeks post second injection) for evaluation of ACF, proliferation, apoptosis, and cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) protein levels. Experimental diets had no effect on the variables measured in saline-injected rats. However, in AOM-injected rats, the experimental diets suppressed (P < or = 0.02) aberrant crypt and high multiplicity ACF (HMACF; P < or = 0.01) formation and the proliferative index (P < or = 0.02) compared with the control diet. Only untreated grapefruit and limonin suppressed (P < or = 0.04) HMACF/cm and expansion (P < or = 0.008) of the proliferative zone that occurred in the AOM-injected rats consuming the control diet. All diets elevated (P < or = 0.05) the apoptotic index in AOM-injected rats, compared with the control diet; however, the greatest enhancement was seen with untreated grapefruit and limonin. Untreated grapefruit and limonin diets suppressed elevation of both iNOS (P < or = 0.003) and COX-2 (P < or = 0.032) levels observed in AOM-injected rats consuming the control diet. Although irradiated grapefruit and naringin suppressed iNOS levels in AOM-injected rats, no effect was observed with respect to COX-2 levels. Thus, lower levels of iNOS and COX-2 are associated with suppression of proliferation and upregulation of apoptosis, which may have contributed to a decrease in the number of HMACF in rats provided with untreated grapefruit and limonin. These results suggest that consumption of grapefruit or limonin may help to suppress colon cancer development.