Department of Biology, University of Alabama at Birmingham, Birmingham, AL, United States.
Department of Biology, University of Alabama at Birmingham, Birmingham, AL, United States.
J Nutr. 2023 Jul;153(7):1959-1973. doi: 10.1016/j.tjnut.2023.05.001. Epub 2023 May 3.
Parental nutritional interventions have considerably affected gametogenesis and embryogenesis, leading to the differential susceptibility of offspring to chronic diseases such as cancer. Moreover, combinatorial bioactive diets are more efficacious in ameliorating epigenetic aberrations in tumorigenesis.
We sought to investigate the transgenerational influence and epigenetic regulation of paternal sulforaphane (SFN)-rich broccoli sprouts (BSp) and epigallocatechin-3-gallate (EGCG)-rich green tea polyphenols (GTPs) consumption in the prevention of estrogen receptor-negative [ER(-)] mammary cancer in transgenic mice.
Human breast cancer cells were used to detect cell viability and epigenetic-related gene expression after treatment with EGCG and/or SFN. Twenty-four C3 or HER2/neu males were randomly assigned into 4 groups and treated with control, 26% BSp (w/w) in food, 0.5% GTPs (w/v) in drinking water or combined BSp and GTPs for 7 wk before mating. Tumor growth of nontreated female pups was monitored weekly for 19 wk (C3) and 25 wk (HER2/neu). Tumor- and epigenetic-related protein expression and enzyme activities in mammary tumors were measured. Sperms were isolated from treated males for RNA sequencing and reduced-representation bisulfite sequencing analysis. Data were analyzed with a 2-factor or 3-factor analysis of variance.
EGCG and SFN inhibited breast cancer cell growth via epigenetic regulation. Combined BSp and GTPs synergistically (combination index < 1) suppressed tumor growth over time (P < 0.001) in 2 mouse models. Key tumor-related proteins were found differentially expressed (P < 0.05) along with epigenetic regulations in offspring mammary tumors. The transcriptome profile of sperm derived from dietary-treated males revealed differentially expressed genes correlated with spermatogenesis and breast cancer progression. DNA methylomes of the sperm and further integrated analysis with transcriptomes indicate that DNA methylation alone may not contribute to sufficient regulation in dietary-treated sperm pronucleus, leading to offspring tumor suppression.
Collectively, paternal consumption of combined BSp and GTPs shows potential for preventing ER(-) mammary cancer through transgenerational effects. J Nutr 2023;xx:xx-xx.
父母的营养干预极大地影响了配子发生和胚胎发生，导致后代对癌症等慢性疾病的易感性存在差异。此外，组合生物活性饮食在改善肿瘤发生中的表观遗传异常方面更有效。
我们旨在研究父代富含萝卜硫素（SFN）的西兰花芽（BSp）和富含表没食子儿茶素没食子酸酯（EGCG）的绿茶多酚（GTP）消费的跨代影响和表观遗传调控，以预防雌激素受体阴性（ER(-)）乳腺癌在转基因小鼠中。
用人乳腺癌细胞检测 EGCG 和/或 SFN 处理后细胞活力和与表观遗传相关的基因表达。24 只 C3 或 HER2/neu 雄性被随机分为 4 组，分别用对照、食物中 26%BSp（w/w）、饮用水中 0.5%GTPs（v/v）或联合 BSp 和 GTPs 处理 7 周，然后交配。未处理雌性幼崽的肿瘤生长每周监测 19 周（C3）和 25 周（HER2/neu）。测量乳腺肿瘤中的肿瘤和与表观遗传相关的蛋白表达和酶活性。从处理后的雄性中分离精子进行 RNA 测序和简化代表性双硫代修饰测序分析。数据采用 2 因素或 3 因素方差分析进行分析。
EGCG 和 SFN 通过表观遗传调控抑制乳腺癌细胞生长。联合 BSp 和 GTPs 随时间推移协同抑制肿瘤生长（P<0.001）在 2 种小鼠模型中。在后代乳腺肿瘤中发现关键的肿瘤相关蛋白表达差异（P<0.05）和表观遗传调控。来自饮食处理雄性的精子转录组谱显示与精子发生和乳腺癌进展相关的差异表达基因。精子的 DNA 甲基组图谱以及与转录组的进一步综合分析表明，DNA 甲基化本身可能不足以调节饮食处理精子原核，从而抑制后代肿瘤。
总的来说，父代同时摄入 BSp 和 GTPs 具有通过跨代效应预防 ER(-)乳腺癌的潜力。J Nutr 2023；xx:xx-xx。
