Abstract 2571: Paternal epigenetic regulation contributes to the prevention of estrogen receptor-negative mammary cancer with combined broccoli sprouts and green tea polyphenols consumption in transgenic mice

Shizhao Li, Huixin Wu, T. Tollefsbol
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Abstract

Breast cancer is one of the leading causes of cancer-related death among women in the United States. It is widely appreciated that abnormal epigenetic alterations act as one of the primary contributors to breast cancer initiation and progression. Parental, including maternal and paternal, nutritional interventions have shown considerable impact on fetal development leading to different susceptibility of offspring to various chronic diseases. Moreover, combinatorial dietary administration to parents could be more efficacious in ameliorating epigenetic aberrations and changing cancer risk in an individual9s later life. The bioactive dietary broccoli sprouts (BSp) and green tea polyphenol (GTP) are important epigenetic modulators that can prevent various cancers. Our study focusses on investigating the effect of paternal dietary BSp and GTP administration on mammary cancer prevention of their offspring. Two spontaneous breast cancer transgenic mouse models, C3(1)/SV40 and Her2/neu, were employed in this study. Male C3(1)/SV40 or Her2/neu transgenic mice were randomly assigned into four groups and treated with: control AIN-93G diet, 26% BSp (w/w) in food pellets, 0.5% GTPs (w/v) in drinking water or combined BSp and GTPs from 3 wks of age until 10 wks of age. Treated male mice of different groups were then mated with non-treated female mice. Female pups were selected after their weaning and tumor growth was monitored weekly until the termination of the experiment. Tumor- and epigenetic-related protein expression and histone modifications (methylation and acetylation) were measured. Our study indicated that paternal BSp or/and GTPs administration suppressed tumor growth, decreased tumor incidence, and delayed tumor latency compared with the control in both mouse models. Overall, paternal dietary intervention displayed more efficacy for mammary tumor prevention in C3(1)/SV40 mice and the combination group in this model also showed synergistically effects. Subsequent analysis with the C3(1)/SV40 mouse tumors demonstrated that paternal BSp or/and GTPs treatments upregulated the expression of tumor suppressor proteins, such as P16 and P53, and down-regulated tumor promoting proteins, such as MYC and BMI1. Moreover, altered DNA methylation, histone methylation and acetylation levels were also observed. These results suggested that paternal exposure to BSp and GTPs may contribute to ER-negative mammary tumor prevention in their offspring through epigenetic regulations and the combined addition of bioactive botanicals could be a more promising approach for coping with breast cancer initiation and progression in humans. Citation Format: Shizhao Li, Huixin Wu, Trygve Tollefsbol. Paternal epigenetic regulation contributes to the prevention of estrogen receptor-negative mammary cancer with combined broccoli sprouts and green tea polyphenols consumption in transgenic mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2571.
摘要/ Abstract摘要:花椰菜芽和绿茶多酚联合摄入转基因小鼠父本表观遗传调控有助于预防雌激素受体阴性乳腺癌
乳腺癌是美国女性癌症相关死亡的主要原因之一。人们普遍认为,异常的表观遗传改变是乳腺癌发生和发展的主要因素之一。父母(包括母亲和父亲)的营养干预对胎儿发育有相当大的影响,导致后代对各种慢性疾病的易感性不同。此外,对父母进行组合膳食管理可能更有效地改善表观遗传畸变和改变个人以后生活中的癌症风险。生物活性膳食中的西兰花芽(BSp)和绿茶多酚(GTP)是预防多种癌症的重要表观遗传调节剂。本研究旨在探讨父亲膳食中添加BSp和GTP对其后代乳腺癌预防的影响。本研究采用C3(1)/SV40和Her2/neu两种转基因小鼠模型。雄性C3(1)/SV40或Her2/neu转基因小鼠随机分为4组,从3周龄至10周龄,分别饲喂对照AIN-93G饲粮、食物颗粒中26% BSp (w/w)、饮用水中0.5% gtp (w/v)或BSp和gtp的组合。然后将不同组的治疗过的雄性小鼠与未治疗过的雌性小鼠交配。断奶后选择雌性幼犬,每周监测肿瘤生长情况,直至实验结束。测量肿瘤和表观遗传相关蛋白表达和组蛋白修饰(甲基化和乙酰化)。我们的研究表明,在两种小鼠模型中,与对照组相比,父本给药BSp或/和GTPs抑制了肿瘤生长,降低了肿瘤发病率,并延迟了肿瘤潜伏期。综上所述,父本饮食干预对C3(1)/SV40小鼠乳腺肿瘤的预防效果更好,该模型中联合组也显示出协同效应。随后对C3(1)/SV40小鼠肿瘤的分析表明,父本BSp或/和gtp处理上调了肿瘤抑制蛋白(如P16和P53)的表达,下调了肿瘤促进蛋白(如MYC和BMI1)的表达。此外,还观察到DNA甲基化、组蛋白甲基化和乙酰化水平的改变。这些结果表明,父亲暴露于BSp和gtp可能通过表观遗传调控有助于后代er阴性乳腺肿瘤的预防,联合添加生物活性植物药物可能是应对人类乳腺癌发生和发展的更有希望的方法。引用格式:李士钊,吴慧新,Trygve Tollefsbol。在转基因小鼠中,结合西兰花芽和绿茶多酚摄入,父本表观遗传调控有助于预防雌激素受体阴性乳腺癌[摘要]。见:美国癌症研究协会2021年年会论文集;2021年4月10日至15日和5月17日至21日。费城(PA): AACR;癌症杂志,2021;81(13 -增刊):2571。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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