Roles of Dietary Bioactive Compounds in Gut Microbiota Modulation and Epigenetic Regulation in the Prevention of Breast Cancer

Abstract

Breast cancer (BC) is the second most common cancer and the second leading cause of cancer death among women in the United States. The average risk of a woman developing BC is about 13% according to American Cancer Society. Various genetic-related risk factors including inherited mutations of genes, and lifestyle-related risk factors such as physical inactivity, obesity, aging, smoking, and air pollution have been studied for cancer prevention and treatment. The currently existing treatment methods such as chemotherapy and neoadjuvant systemic therapy can induce adverse effects on patients. Therefore, cancer prevention has been of great interest to the society. Numerous studies show that dietary intervention prevents BC occurrence and benefits overall survival. Early-life dietary intervention confers more efficacious and beneficial effects. Previous studies have shown that a diet rich in antioxidant and anti-inflammatory bioactive compounds have BC prevention effect. These bioactive compounds include sulforaphane (SFN), an isothiocyanate extracted from broccoli sprouts (BSp); epigallocatechin-3-gallate (EGCG), an antioxidant component in green-tea polyphenols (GTP); inulin (IN), naturally occurring polysaccharides produced by many plants and well-known dietary fibers. The mechanism of their cancer prevention effect has not been fully discovered and revealed. We investigated the efficacy of early-life dietary intervention with a combination of BSp and GTPs in preventing estrogen receptor negative (ER-) BC. Combinatorial treatment synergistically suppressed the tumor growth and induced the expression of tumor suppressors and cell cycle arrest. Phytochemicals, vitamins, and dietary fibers are active anticancer components in plant-based diets. Gut microbes play an important role in digesting and absorbing nutrients, and secreting metabolites and byproducts in the host. The supplementation of dietary fiber inulin at early-life stage was studied in ER- BC prevention. The supplementation changed gut microbial composition, increased short-chain fatty acids (SCFAs) level in the plasma, and induced protective epigenetic regulations. The combinatorial dietary treatment of BSp and inulin was also studied. Their synergistic BC prevention effect was mediated by the induction of AKT-PI3K/mTOR pathway, apoptosis, and cell cycle arrest. Overall, our studies provide preliminary evidence in understanding the mechanisms of bioactive dietary compounds in ER- BC prevention. Administering food-derived anticancer agents may be a promising strategy for cancer prevention and treatment.