Wu Huixin, Witt Brittany L, van der Pol William J, Morrow Casey D, Duck Lennard W, Tollefsbol Trygve O
Department of Biology, College of Arts and Sciences, University of Alabama at Birmingham, Birmingham, AL 35233, USA.
Department of Microbiology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35205, USA.
Nutrients. 2025 Jun 17;17(12):2023. doi: 10.3390/nu17122023.
Breast cancer (BC) is the second most common cancer among women in the United States. It has been estimated that one in eight women will be diagnosed with breast cancer in her lifetime. Various BC risk factors, such as age, physical inactivity, and smoking, play a substantial role in BC occurrence and development. Early life dietary intervention with plant-based bioactive compounds has been studied for its potential role in BC prevention. Sulforaphane (SFN), an isothiocyanate, is an antioxidant and anti-inflammatory agent extracted from broccoli sprouts (BSp) and other plants. Dietary supplementation of SFN suppresses tumor growth by inducing protective epigenetic changes and inhibiting cancer cell proliferation. Inulin, as a dietary fiber, has been studied for alleviating GI discomfort and weight loss by promoting the growth of beneficial bacteria in the gut. Early-life combinatorial treatment with both phytochemical SFN and potential prebiotic agent inulin at lower and safer dosages may confer more efficacious and beneficial effects in BC prevention. Transgenic mice representing estrogen receptor-negative BC were fed 26% (/) BSp and 2% (/) inulin supplemented in food and water, respectively. The combinatorial treatment inhibited tumor growth, increased tumor onset latency, and synergistically reduced tumor weight. Gut microbial composition was analyzed between groups, where , , and significantly increased, while , , and 1 significantly decreased in the combinatorial group compared with the control group. Furthermore, combinatorial treatment induced a protective epigenetic effect by inhibiting histone deacetylases (HDACs) and DNA methyltransferases (DNMTs). Intermediates in the AKT/PI3K/MTOR pathway were significantly suppressed by the combinatorial treatment, including PI3K p85, p-AKT, p-PI3K p55, MTOR, and NF-κB. Cell cycle arrest and programmed cell death were induced by the combinatorial treatment via elevating the expression of cleaved-caspase 3 and 7 and inhibiting the expressions of CDK2 and CDK4, respectively. Orally administering attenuated tumor growth and induced apoptosis in a syngeneic triple-negative breast cancer (TNBC) mouse model. Overall, the findings suggest that early-life dietary combinatorial treatment contributed to BC prevention and may be a potential epigenetic therapy that serves as an adjunct to other traditional neoadjuvant therapies.
乳腺癌（BC）是美国女性中第二常见的癌症。据估计，八分之一的女性在其一生中会被诊断出患有乳腺癌。各种乳腺癌风险因素，如年龄、缺乏身体活动和吸烟，在乳腺癌的发生和发展中起着重要作用。早期通过植物性生物活性化合物进行饮食干预对预防乳腺癌的潜在作用已得到研究。萝卜硫素（SFN）是一种异硫氰酸盐，是从西兰花芽苗菜（BSp）和其他植物中提取的抗氧化剂和抗炎剂。饮食中补充SFN可通过诱导保护性表观遗传变化和抑制癌细胞增殖来抑制肿瘤生长。菊粉作为一种膳食纤维，已被研究用于通过促进肠道有益细菌的生长来缓解胃肠道不适和减轻体重。在早期用较低且更安全剂量的植物化学物质SFN和潜在的益生元菊粉进行联合治疗，可能在预防乳腺癌方面产生更有效和有益的效果。给代表雌激素受体阴性乳腺癌的转基因小鼠分别喂食食物和水中添加26%（/）的BSp和2%（/）的菊粉。联合治疗抑制了肿瘤生长，延长了肿瘤发病潜伏期，并协同减轻了肿瘤重量。对各组之间的肠道微生物组成进行了分析，与对照组相比，联合治疗组中 、 和 显著增加，而 、 和 1 显著减少。此外，联合治疗通过抑制组蛋白脱乙酰酶（HDACs）和DNA甲基转移酶（DNMTs）诱导了保护性表观遗传效应。联合治疗显著抑制了AKT/PI3K/MTOR途径中的中间体，包括PI3K p85、p-AKT、p-PI3K p55、MTOR和NF-κB。联合治疗通过分别提高裂解的半胱天冬酶3和7的表达并抑制CDK2和CDK4的表达来诱导细胞周期停滞和程序性细胞死亡。在同基因三阴性乳腺癌（TNBC）小鼠模型中口服 可减缓肿瘤生长并诱导细胞凋亡。总体而言，研究结果表明，早期饮食联合治疗有助于预防乳腺癌，可能是一种潜在的表观遗传疗法，可作为其他传统新辅助疗法的辅助手段。
