Faculty of Nutrition, Texas A&M University, College Station, TX 77843-3143, USA.
Exp Biol Med (Maywood). 2010 Jun;235(6):710-7. doi: 10.1258/ebm.2010.009359.
Epidemiological evidence suggests that a diet abundant in fruits and vegetables may protect against colon cancer. Bioactive compounds, including flavonoids and limonoids, have been shown to possess antiproliferative and antitumorigenic effects in various cancer models. This experiment investigated the effects of four citrus flavonoids and one limonoid mixture at the promotion stage of chemically induced colon cancer in rats. Male Sprague-Dawley rats (n = 10 rats/group) were randomly allocated to one of six diets formulated to contain 0.1% apigenin, 0.02% naringenin, 0.1% hesperidin, 0.01% nobiletin, 0.035% limonin glucoside/obacunone glucoside mixture or a control diet (0% flavonoid/limonoid). Rats received experimental diets for 10 weeks and were injected with azoxymethane (15 mg/kg) at weeks 3 and 4. Excised colons were evaluated for aberrant crypt foci (ACF) formation, colonocyte proliferation (proliferating cell nuclear antigen assay), apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labeling assay) and expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) (immunoblotting). When compared with the control diet, apigenin lowered the number of high multiplicity ACF (HMACF >4 aberrant crypts/focus) by 57% (P < 0.05), while naringenin lowered both the number of HMACF by 51% (P < 0.05) and the proliferative index by 32% (P < 0.05). Both apigenin and naringenin increased apoptosis of luminal surface colonocytes (78% and 97%, respectively; P < 0.05) when compared with the control diet. Hesperidin, nobiletin and the limonin glucoside/obacunone glucoside mixture did not affect these variables. The colonic mucosal protein levels of iNOS or COX-2 were not different among the six diet groups. The ability of dietary apigenin and naringenin to reduce HMACF, lower proliferation (naringenin only) and increase apoptosis may contribute toward colon cancer prevention. However, these effects were not due to mitigation of iNOS and COX-2 protein levels at the ACF stage of colon cancer.
流行病学证据表明，富含水果和蔬菜的饮食可能有助于预防结肠癌。生物活性化合物，包括类黄酮和柠檬苦素，已被证明在各种癌症模型中具有抗增殖和抗肿瘤作用。本实验研究了四种柑橘类黄酮和一种柠檬苦素混合物在化学诱导的大鼠结肠癌促进阶段的作用。雄性 Sprague-Dawley 大鼠（每组 10 只大鼠）随机分配到 6 种饮食配方中的一种，这些配方分别含有 0.1%芹菜素、0.02%柚皮苷、0.1%橙皮苷、0.01%诺必灵、0.035%柠檬苦素葡萄糖苷/obacunone 葡萄糖苷混合物或对照饮食（0%类黄酮/柠檬苦素）。大鼠接受实验饮食 10 周，并在第 3 周和第 4 周接受氧化偶氮甲烷（15mg/kg）注射。评估切除的结肠中异常隐窝病灶（ACF）的形成、结肠细胞增殖（增殖细胞核抗原测定）、凋亡（末端脱氧核苷酸转移酶 dUTP 缺口末端标记测定）和诱导型一氧化氮合酶（iNOS）和环氧化酶-2（COX-2）的表达（免疫印迹）。与对照饮食相比，芹菜素使高倍数 ACF（HMACF>4 个异常隐窝/病灶）的数量减少了 57%（P<0.05），而柚皮苷使 HMACF 的数量减少了 51%（P<0.05）和增殖指数减少了 32%（P<0.05）。与对照饮食相比，芹菜素和柚皮苷均使腔面结肠细胞的凋亡增加了 78%和 97%（P<0.05）。橙皮苷、诺必灵和柠檬苦素葡萄糖苷/obacunone 葡萄糖苷混合物均未影响这些变量。六种饮食组的结肠黏膜 iNOS 或 COX-2 的蛋白水平没有差异。膳食中芹菜素和柚皮苷降低 HMACF、降低增殖（仅柚皮苷）和增加凋亡的能力可能有助于预防结肠癌。然而，这些作用并非由于在结肠癌的 ACF 阶段减轻 iNOS 和 COX-2 蛋白水平所致。
