A chemoprotective fish oil/pectin diet enhances apoptosis via Bcl-2 promoter methylation in rat azoxymethane-induced carcinomas.
A chemoprotective fish oil/pectin diet enhances apoptosis via Bcl-2 promoter methylation in rat azoxymethane-induced carcinomas.
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DOI：
10.1258/ebm.2012.012244
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发表时间：
2012-12
期刊：
影响因子：
--
通讯作者：
Lupton JR
中科院分区：
文献类型：
--
作者：
Cho Y;Turner ND;Davidson LA;Chapkin RS;Carroll RJ;Lupton JR
我们已经证明，相对于对照组（玉米油和纤维素[CO/C]），含有鱼油和果胶（FO/P）的饮食部分通过诱导DNA损伤的结肠细胞凋亡来降低结肠肿瘤发病率。相对于FO/P，CO/C促进抗凋亡调节剂Bcl-2的结肠细胞表达，并且Bcl-2启动子甲基化在结肠癌中改变。为了确定与CO/C相比，FO/P是否通过增强结肠肿瘤中的启动子甲基化来限制Bcl-2表达，我们检测了氧化偶氮甲烷（AOM）注射大鼠中Bcl-2启动子甲基化、mRNA水平、结肠细胞凋亡和结肠肿瘤发病率。大鼠提供含有FO/P或CO/C的饮食，并在AOM注射后16周和34周终止。从多聚甲醛固定的结肠肿瘤和未受累组织中分离的DNA经亚硫酸氢盐修饰，并通过定量逆转录酶-聚合酶链反应扩增，以评估Bcl-2胞嘧啶-鸟苷岛的DNA甲基化。与CO/C组相比，FO/P组肿瘤组织Bcl-2基因启动子甲基化水平升高（P = 0.009），结肠细胞凋亡增加（P = 0.020）。Bcl-2基因甲基化与Bcl-2 mRNA表达水平呈负相关。我们的结论是，饮食FO/P促进细胞凋亡的一部分，通过增强Bcl-2启动子甲基化。这些Bcl-2启动子甲基化反应，在体内测量，有助于我们理解的化学预防结肠癌的饮食含有FO/P的机制。
We have demonstrated that diets containing fish oil and pectin (FO/P) reduce colon tumor incidence relative to control (corn oil and cellulose [CO/C]) in part by inducing apoptosis of DNA-damaged colon cells. Relative to FO/P, CO/C promotes colonocyte expression of the antiapoptotic modulator, Bcl-2, and Bcl-2 promoter methylation is altered in colon cancer. To determine if FO/P, compared with CO/C, limits Bcl-2 expression by enhancing promoter methylation in colon tumors, we examined Bcl-2 promoter methylation, mRNA levels, colonocyte apoptosis and colon tumor incidence in azoxymethane (AOM)-injected rats. Rats were provided diets containing FO/P or CO/C, and were terminated 16 and 34 weeks after AOM injection. DNA isolated from paraformaldehyde-fixed colon tumors and uninvolved tissue was bisulfite modified and amplified by quantitative reverese transcriptase-polymerase chain reaction to assess DNA methylation in Bcl-2 cytosine–guanosine islands. FO/P increased Bcl-2 promoter methylation (P = 0.009) in tumor tissues and colonocyte apoptosis (P = 0.020) relative to CO/C. An inverse correlation between Bcl-2 DNA methylation and Bcl-2 mRNA levels was observed in the tumors. We conclude that dietary FO/P promotes apoptosis in part by enhancing Bcl-2 promoter methylation. These Bcl-2 promoter methylation responses, measured in vivo, contribute to our understanding of the mechanisms involved in chemoprevention of colon cancer by diets containing FO/P.
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影响因子：
8.8
作者：
通讯作者：
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影响因子：
4.2
作者：
Cho, Youngmi;Kim, Hyemee;Lupton, Joanne R.
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Lupton, Joanne R.
影响因子：
78.5
作者：
Issa, JP
通讯作者：
Issa, JP
影响因子：
4.2
作者：
Chang, WCL;Chapkin, RS;Lupton, JR
通讯作者：
Lupton, JR
影响因子：
4.7
作者：
Davidson, Laurie A.;Wang, Naisyin;Chapkin, Robert S.
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