RESUMO
Breast cancer recurrence continues to pose a major clinical problem, despite significant advancements in early diagnosis and an aggressive mode of treatment. This study aimed at investigating the anticancer activity of Oroxylum indicum extract (OIE) by assessing cell proliferation, cell migration, and angiogenesis in metastatic breast cancer MDA-MB-231 cell lines. This study also estimated the phytochemical profiles of OIE by LC-QTOF-MS. The extract was found to contain six identified flavonoid substances, and baicalein was the most abundant substance in the extract. Cell proliferation capacity was performed by cell counting kit-8 (CCK-8) and colony formation assays. The effect of OIE on cell migration was determined using wound healing and transwell assays. Meanwhile, MDA-MB-231-induced angiogenesis on chick chorioallantoic membrane (CAM) was applied to investigate the ex vivo antiangiogenesis activity of the extracts. OIE at concentrations lower than 600 µg/mL had no cytotoxic effects against MDA-MB-231 cells. OIE was found to inhibit the long-term colony formation ability of MDA-MB-231 cells in a concentration-dependent manner. Antimigration and antiangiogenesis activities were further investigated using noncytotoxic concentrations of OIE ranging from 25 to 150 µg/mL. OIE greatly reduced the migration of MDA-MB-231 breast cancer cells in a dose-dependent manner. OIE significantly suppressed the MDA-MB-231-induced angiogenesis, and there was no substantial toxic effect on natural angiogenesis. Interestingly, the concentration of OIE at 150 µg/mL was as practically potent as pazopanib, the positive anticancer drug, at 4.37 µg/mL in inhibiting MDA-MB-231 cell migration and angiogenesis induced by these cells. Therefore, the inhibitory effects of OIE in cell proliferation and cell migration, together with antiangiogenesis in MDA-MB-231 breast cancer cells, suggesting that OIE has the potential to be a novel adjunct candidate for breast cancer chemotherapeutic agents.
RESUMO
Currently, human Wharton's jelly-derived mesenchymal stem cells (hWJ-MSCs) are an attractive source of stem cells for cell-based therapy, owing to their ability to undergo self-renewal and differentiate into all mesodermal, some neuroectodermal, and endodermal progenies, including hepatocytes. Herein, this study aimed to investigate the effects of sodium butyrate (NaBu), an epigenetic regulator that directly inhibits histone deacetylase, on hepatic endodermal lineage differentiation of hWJ-MSCs. NaBu, at 1 mM, optimally promoted endodermal differentiation of hWJ-MSCs, along with epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) supplementation (EGF + bFGF + 1 mM NaBu). CXCR4, HNF3ß, SOX17 (endodermal), and GATA6 (mesendodermal) mRNAs were also up-regulated (p < 0.001). Immunocytochemistry and a Western blot analysis of SOX17 and HNF3ß confirmed that the EGF + bFGF + 1 mM NaBu condition was appropriately pre-treated with hWJ-MSCs before hepatogenic differentiation. Furthermore, the hepatogenic medium + NaBu pre-treatment up-regulated hepatoblast (AFP and HNF3ß) and hepatic (CK18 and ALB) markers, and increased the proportion of mature hepatocyte functions, including G6P, C/EBPα, and CYP2B6 mRNAs, glycogen storage and urea secretion. The hepatogenic medium + NaBu in the pre-treatment step can induce hWJ-MSC differentiation toward endodermal, hepatoblastic, and hepatic lineages. Therefore, the hepatogenic medium + NaBu pre-treatment for differentiating hWJ-MSCs could represent an alternative protocol for cell-based therapy and drug screening in clinical applications.