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

Abstract

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.

Anti-Hepatocellular-Cancer Activity Exerted by β-Sitosterol and β-Sitosterol-Glucoside from Indigofera zollingeriana Miq

“…13 C-NMR (125 MHz, DMSO-d 6 ), δ(ppm): (δ C 140.3; C-5); (δ C 122.0; C-6); (δ C 101.1; C-1‘); (δ C 79.1; C-3),(δ C 73.5; C-2‘), (δ C 76.4; C-3‘), (δ C 70.2; C-4′), (δ C 75.7; C-5′), (δ C 61.8; C-6′), sp 3 (δ C 36.6; C-10), (δ C 42.3; C-13), (δ C 31.8; C-8), (δ C 50.2; C-9), (δ C 56.7; C-14), (δ C 56.0; C-17), (δ C 36.1; C-20), (δ C 45.9; C-24), (δ C 29.2; C-25), (δ C 37.2; C-1), (δ C 29.5; C-2), (δ C 38.6; C-4), (δ C 31.8; C-7), (δ C 21.0; C-11), (δ C 39.7; C-12), (δ C 24.2; C-15), (δ C 28.1; C-16), (δ C 33.9; C-22), (δ C 26.1; C-23), (δ C 23.0; C-28), (δ C 11.7; C-18), (δ C 19.1; C-19), (δ C 18.6; C-21), (δ C 19.6; C-26), (δ C 18.9; C-27), (δ C 11.8; C-29). These findings were in line with the published findings [ 30 , 31 ]. Figure 3 reveals the chemical structure of the InE compound isolated from I. zollingeriana (see also Figures S4–S6 for the spectra).…”

Participation of MicroRNAs in the Treatment of Cancer with Phytochemicals

“…In breast cancer, miR-10a was determined to interrupt PI3K/Akt activation via targeting phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), hence acting as a tumor-suppressive miRNA to suppress breast cancer progression [ 231 ]. In line with this, new findings indicated that β-sitosterol- d -glucoside upregulates miR-10a levels and displays anti-cancer activity through inactivating PI3K/Akt signaling [ 31 ] ( Figure 1 and Table 4 ). Treatment with β-sitosterol- d -glucoside significantly diminishes cancer growth in mouse xenograft models of breast cancer [ 31 ].…”

“…In line with this, new findings indicated that β-sitosterol- d -glucoside upregulates miR-10a levels and displays anti-cancer activity through inactivating PI3K/Akt signaling [ 31 ] ( Figure 1 and Table 4 ). Treatment with β-sitosterol- d -glucoside significantly diminishes cancer growth in mouse xenograft models of breast cancer [ 31 ].…”

Daucosterol linolenate from Sweet Potato Suppresses MCF7-Xenograft-Tumor Growth through Regulating PI3K/AKT Pathway

“…In this study, we isolated DLA, a fatty acid ester of daucosterol. In previous studies, daucosterol has been shown to inhibit the proliferation of various cancer cell lines, including breast cancer [17]. Esmaeili et al reported that daucosterol activated apoptosis in human breast adenocarcinoma cells via up-regulating PTEN and down-regulating PI3K/AKT pathway [18].…”