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Chemoprevention against colon cancer by dietary intake of sulforaphane

机译：通过饮食摄入萝卜硫烷对大肠癌的化学预防

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Background: Sulforaphane (SFN) is a phytochemical compound which belongs to isothiocyanates family found in abundance in broccoli sprouts. SFN induces a variety of antioxidant enzymes via NF-E2-related factor 2-Kelch-like ECH-associated protein 1-mediated pathway, thereby protecting cells from injury induced by various kinds of oxidative stresses. We have previously shown that SFN protects gastric mucosa from oxidative injury induced by H. pylori infection. SFN also down-regulates histone deacetylase (HDAC) activity, thereby inducing apoptosis and inhibiting proliferation of tumor cells in variety of tissues. On the other hand, the incidence of colon cancer has increased in Japan.Aim: Since numerous epidemiological studies have shown that colon cancer is inversely associated with intake of anti-oxidant vegetables, this study examines whether daily intake of SFN prevents colon tumorigenesis in mice and human subjects.Methods1. Effects of SFN on Colonic tumorigenesis in Mice Treated with Chemical Carcinogen: Effects of SFN on colonic tumorigenesis were examined in the ICR male mice, pretreated with a chemical carcinogen, azoxymethane (AOM) (15 mg/kg). The mice treated with AOM for 3 or 6 times were fed for 8 or 24 weeks with or without sulforaphane glucosinolates (SGS: 2,200 ppm/kg/day), which is a precursor of SFN. Effects of SGS treatment on formation of the microscopic aberrant crypt foci (ACF) and the macroscopic tumors in colonic mucosa were evaluated.2. Effects of SFN on formation of Colonic ACF in patients with colonic adenoma: Effects of intake of raw broccoli sprouts (BS), 50 g/day containing 220 mg SGS every other day, for 6 months on changes in the number of ACF in rectal mucosa was examined by colonoscopy in patients with colonic adenoma.3. Effects of SFN on intestinal microbiota in human subjects: Effects of dietary intake of raw BS, 20 g/day, which contains 88 mg SGS every other day, for 2 weeks on intestinal microbiota in healthy volunteers was assessed by measuring composition of stool bacteria, using a method of terminal restriction fragment length polymorphism flora analysis. In human studies, alfalfa sprouts, which contains no SFN, was used as a placebo control.Results: 1. Daily administration of SGS suppressed formation of microscopic ACF and macroscopic colonic tumors in the AOM-pretreated mice in vivo. 2. Intake of BS for 6 months tended to decrease the number of colonic ACF in patients with colonic adenoma. 3. Intake of BS for 2 weeks increased percentages of Bifidobacterium and Clostridium XVIa, which has been shown to enhance protection of colonic mucosa by increasing butyrate production in colonic lumen.Conclusions: 1. Daily intake of SFN affords chemoprotection against colonic tumors in the mice treated with a chemical carcinogen. 2. The present study further suggests that, in addition to previously reported mechanisms, changes in the intestinal microbiota by SFN intake may also play a role in chemoprevention against colon cancer. Further studies are required to prove this possibility.
机译：背景：萝卜硫素（SFN）是一种植物化学化合物，属于花椰菜芽中大量存在的异硫氰酸酯家族。 SFN通过NF-E2相关因子2-Kelch样ECH相关蛋白1介导的途径诱导多种抗氧化酶，从而保护细胞免受各种氧化应激诱导的损伤。先前我们已经表明，SFN保护胃粘膜免受幽门螺杆菌感染引起的氧化损伤。 SFN还下调组蛋白脱乙酰基酶（HDAC）的活性，从而诱导凋亡并抑制多种组织中肿瘤细胞的增殖。另一方面，在日本，结肠癌的发病率有所上升。目的：由于大量流行病学研究表明，结肠癌与抗氧化蔬菜的摄入呈负相关，因此该研究探讨了每天摄入SFN是否可以预防小鼠结肠癌的发生。方法1。 SFN对用化学致癌物治疗的小鼠结肠肿瘤发生的影响：在用化学致癌物，乙氧基甲烷（AOM）（15 mg / kg）预处理的ICR雄性小鼠中检查了SFN对结肠肿瘤发生的影响。用AOM处理3或6次的小鼠在有或没有萝卜硫烷硫代葡萄糖苷（SGS：2,200 ppm / kg /天）的情况下饲养8或24周，这是SFN的前体。观察了SGS治疗对结肠黏膜微观异常隐窝灶（ACF）形成和肉眼可见肿瘤的影响。2。 SFN对结肠腺瘤患者结肠ACF形成的影响：每天服用50 g /天，每隔一天摄入220 mg SGS的花椰菜芽（BS）6个月对直肠粘膜ACF数量变化的影响结肠镜检查结肠镜检查3。 SFN对人类受试者肠道菌群的影响：通过测量粪便细菌的组成，评估健康志愿者中每日摄入20 g /天，隔日含有88 mg SGS的未加工BS的饮食对肠道菌群的影响，持续2周。采用末端限制性片段长度多态性菌群分析方法。在人体研究中，不含SFN的苜蓿芽被用作安慰剂对照。结果：1.每天施用SGS可抑制AOM预处理的小鼠体内微观ACF和宏观结肠肿瘤的形成。 2. BS摄入6个月倾向于减少结肠腺瘤患者结肠ACF的数量。 3.摄入BS 2周后，双歧杆菌和梭状芽胞杆菌XVIa的百分比增加，这已被证明可通过增加结肠腔内丁酸的产生来增强对结肠粘膜的保护。结论：1.每天摄入SFN可对小鼠的结肠肿瘤提供化学保护作用。用化学致癌物治疗。 2.本研究进一步表明，除先前报道的机制外，SFN摄入引起的肠道菌群变化也可能在化学预防结肠癌中起作用。需要进一步的研究来证明这种可能性。

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