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Anti-breast-Cancer Activity Exerted by β-Sitosterol-d-glucoside from Sweet Potato via Upregulation of MicroRNA-10a and via the PI3K–Akt Signaling Pathway

Xu, Heshan, Li, Yuanfeng, Han, Bing, Li, Zhaoxing, Wang, Bin, Jiang, Pu, Zhang, Jian, Ma, Wenyu, Zhou, Deqi, Li, Xuegang, Ye, Xiaoli
Journal of agricultural and food chemistry 2018 v.66 no.37 pp. 9704-9718
antineoplastic activity, apoptosis, breast neoplasms, caspases, cell lines, cell viability, cytotoxicity, flow cytometry, mice, mitochondria, mortality, phosphatidylinositol 3-kinase, phytosterols, protein content, signal transduction, staining, sweet potatoes, therapeutics, women
Breast cancer (BC) is a prominent source of cancer mortality in women throughout the world. β-Sitosterol-d-glucoside (β-SDG), a newly isolated phytosterol from sweet potato, possibly displays potent anticancer activity. However, the probable anticancer mechanisms involved are still unclear. This study sought to study how β-SDG from sweet potato affects two BC cell lines (MCF7 and MDA-MB-231) and nude mice bearing MCF7-induced tumors. In addition, we assessed how β-SDG affects tumor suppressor miR-10a and PI3K–Akt signaling in BC cells. Cell viability and proliferation were determined via MTT and colony-formation assays, and apoptosis was quantified by Hoechst staining and flow cytometry. In addition, miR-10a expression and apoptosis-related protein levels were measured. Our study indicated that β-SDG exhibited cytotoxic activities on MCF7 and MDA-MB-231 cells via inducing apoptosis and activating caspase proteases in these cells. Furthermore, the experimental results in nude mice bearing MCF7-induced tumors demonstrated that oral β-SDG administration at medium (60 mg/kg) or high (120 mg/kg) doses was sufficient to substantially impair the growth of tumors and to decrease the levels of CEA, CA125, and CA153 by 64.71, 74.64, and 85.32%, respectively, relative to those of the controls (P < 0.01). β-SDG was further found to regulate the expression of PI3K, p-Akt, Bcl-2-family members, and other factors involved in the PI3K–Akt-mediated mitochondrial signaling pathway via the tumor suppressor miR-10a. These findings indicated that β-SDG suppresses tumor growth by upregulating miR-10a expression and inactivating the PI3K–Akt signaling pathway. Furthermore, β-SDG could be developed as a potential therapeutic agent against MCF7-cell-related BC.