Temporal efficacy of a sulforaphane-based broccoli sprout diet in prevention of breast cancer through modulation of epigenetic mechanisms

摘要

Breast cancer is the most common cancer and the second leading cause of cancer 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 in utero. 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 to 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.