Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, Alabama.
Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama.
Cancer Prev Res (Phila). 2018 Aug;11(8):451-464. doi: 10.1158/1940-6207.CAPR-17-0423. Epub 2018 May 15.
Breast cancer is the most common cancer and the second leading cause of cancer-related death among women. An important risk factor for breast cancer is individual genetic background, which is initially generated early in human life, for example, during the processes of embryogenesis and fetal development Bioactive dietary components such as sulforaphane (SFN), an isothiocyanate from cruciferous vegetables including broccoli sprouts (BSp), cabbage, and kale, has been shown to reduce the risk of developing many common cancers through regulation of epigenetic mechanisms. Our study indicates a prenatal/maternal BSp dietary treatment exhibited maximal preventive effects in inhibiting breast cancer development compared with postnatal early-life and adult BSp treatments in two transgenic mouse models that can develop breast cancer. Postnatal early-life BSp treatment starting prior to puberty onset showed protective effects in prevention of breast cancer but was not as effective as the prenatal/maternal BSp treatment. However, adulthood-administered BSp diet did not reduce mammary tumorigenesis. Our results suggest that the prenatal/maternal BSp bioactive natural plant product may impact early embryonic development by regulating global differential gene expression through affecting epigenetic profiles resulting in differential susceptibility to breast cancer later in life. These results suggest that a temporal exposure to epigenetic-modulating dietary components such as cruciferous vegetables could be a key factor for maximizing chemopreventive effects on human breast cancer. This study may lead to translational breast cancer chemopreventive potential by appropriate administration of key dietary components leading to early breast cancer prevention in humans. .
乳腺癌是最常见的癌症,也是女性癌症相关死亡的第二大主要原因。乳腺癌的一个重要危险因素是个体遗传背景,它最初是在人类生命早期产生的,例如在胚胎发生和胎儿发育过程中。生物活性膳食成分,如十字花科蔬菜中的异硫氰酸酯(SFN),如西兰花芽(BSp)、卷心菜和羽衣甘蓝,已被证明通过调节表观遗传机制来降低许多常见癌症的风险。我们的研究表明,与产后早期生命和成年 BSp 治疗相比,两种可发生乳腺癌的转基因小鼠模型中,产前/母体 BSp 饮食治疗在抑制乳腺癌发展方面表现出最大的预防效果。在青春期前开始的产后早期生命 BSp 治疗显示出预防乳腺癌的保护作用,但不如产前/母体 BSp 治疗有效。然而,成年期给予 BSp 饮食并不能减少乳腺肿瘤发生。我们的结果表明,产前/母体 BSp 生物活性天然植物产物可能通过影响表观遗传谱来调节全局差异基因表达,从而影响对生命后期乳腺癌的易感性,从而影响早期胚胎发育。这些结果表明,对十字花科蔬菜等调节表观遗传的膳食成分进行时间暴露可能是最大限度发挥人类乳腺癌化学预防效果的关键因素。通过适当给予关键膳食成分,本研究可能为人类早期乳腺癌预防带来转化性的乳腺癌化学预防潜力。