Dietary administration with prenyloxycoumarins, auraptene and collinin, inhibits colitis-related colon carcinogenesis in mice
Dietary administration with prenyloxycoumarins, auraptene and collinin, inhibits colitis-related colon carcinogenesis in mice
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DOI：
10.1002/ijc.21719
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发表时间：
2006-06-15
影响因子：
6.4
通讯作者：
Tanaka, Takuji
中科院分区：
文献类型：
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作者：
Kohno, Hiroyuki;Suzuki, Rikako;Tanaka, Takuji
我们先前报道了异戊烯氧基香豆素金萝卜素在化学诱导的啮齿动物消化道、肝脏和膀胱癌发生中的化学预防能力。本研究旨在确定饮食喂养金萝卜素及其相关的异戊烯氧基香豆素collinin是否可以抑制结肠炎相关的小鼠结肠癌的发生。将含有2个剂量水平（0.01和0.05%）的化合物的实验饮食饲喂雄性CD-1（ICR）小鼠17周，所述小鼠以单次腹膜内注射氧化偶氮甲烷（AOM，40 mg/kg体重）开始，并通过在饮用水中的1%（w/v）DSS促进7天。20周后，通过计数结肠肿瘤的发生率和多样性以及增殖细胞核抗原（PCNA）标记指数、凋亡指数、环氧合酶（考克斯）-2、诱导型一氧化氮（iNOS）和硝基酪氨酸在结肠上皮恶性肿瘤中的免疫组化表达来评估其抑瘤作用。在两种剂量下，用auraptene或collinin喂养显著抑制结肠腺癌的发生。此外，金萝卜素或collinin可显著降低腺癌中PCNA、考克斯-2、iNOS和硝基酪氨酸的阳性率，而增加结肠恶性肿瘤的凋亡指数。我们的研究结果可能表明，某些异戊烯氧基香豆素，如auraptene和collinin，可以作为一种有效的药物对结肠炎相关的结肠癌的发展在啮齿动物。(c)2006 Wiley-Liss，Inc.
We previously reported the chemopreventive ability of a prenyloxycoumarin auraptene in chemically induced carcinogenesis in digestive tract, liver and urinary bladder of rodents. The current study was designed to determine whether dietary feeding of auraptene and its related prenyloxycoumarin collinin can inhibit colitis-related mouse colon carcinogenesis. The experimental diets, containing the compounds at 2 dose levels (0.01 and 0.05%), were fed for 17 weeks to male CD-1 (ICR) mice that were initiated with a single intraperitoneal injection of azoxymethane (AOM, 40 mg/kg body weight) and promoted by 1% (w/v) DSS in drinking water for 7 days. Their tumor inhibitory effects were assessed at week 20 by counting the incidence and multiplicity of colonic neoplasms and the immunohistochemical expression of proliferating cell nuclear antigen (PCNA)-labeling index, apoptotic index, cyclooxygenase (COX)-2, inducible nitric oxide (iNOS) and nitrotyrosine in colonic epithelial malignancy. Feeding with auraptene or collinin, at both doses, significantly inhibited the occurrence of colonic adenocarcinoma. In addition, feeding with auraptene or collinin significantly lowered the positive rates of PCNA, COX-2, iNOS and nitrotyrosine in adenocarcinomas, while the treatment in creased the apoptotic index in colonic malignancies. Our findings may suggest that certain prenyloxycoumarins, such as auraptene and collinin, could serve as an effective agent against colitis-related colon cancer development in rodents. (c) 2006 Wiley-Liss, Inc.