RESUMEN
Different structural composition ratios of sucrose stearates with hydrophilic-hydrophobic balance (HLB) values ranging from 1 to 16 on lipolysis in emulsion were investigated using a simulated gastrointestinal tract (GIT). Results showed a direct correlation between the HLB values of sucrose stearates and the lipolysis rate of emulsions, and a lower HLB value led to diminished lipolysis in the GIT simulation model. Mechanism study indicated that poor emulsifying capacity of sucrose stearates and lipolysis of sucrose stearates with lower HLB value inhibited the digestive behavior of oil. In addition, monoester was mainly hydrolyzed in the gastric phase, whereas sucrose polyesters caused lipolysis in the intestinal phase using an in vitro digestive model and HPLC analysis, further suppressing lipid digestion. Furthermore, a decrease in cell cytotoxicity and proinflammatory effects on Caco-2 and Raw264.7 were observed post-digestion, respectively. This work offers important insights into the effects of the degree of esterification of sucrose stearate on lipid digestion behavior in oil-in-water emulsions.
RESUMEN
BACKGROUND: Recently, a novel therapy to treat cancer has been to target cancer stem-like cells (CSCs). The aim of this study was to investigate the effect of solasodine, a steroidal alkaloid isolated from Solanum incanum L., on MCF7 CSCs and to understand the compound's underlying mechanism of action. METHOD: A tumorsphere formation assay was used to evaluate the effects of solasodine on the proliferation and self-renewal ability of MCF7 CSCs. The level of expression of proteins associated with cancer stemness markers and Hh signaling mediators was determined. The interaction between solasodine and Gli1 was calculated by molecular docking and further demonstrated by cellular thermal shift assay. RESULTS: Solasodine significantly decreased the proliferation of MCF7 tumorspheres and showed a stronger cytotoxicity on breast cancer cells with higher levels of Gli1 expression. The results showed that the levels of CD44 and ALDH1 expression were suppressed. Furthermore, expression of CD24 was enhanced by solasodine, via a mechanism that involved dampening Gli1 expression and blocking the nuclear translocation of this protein in MCF7 tumorspheres. Computational studies predicted that solasodine showed a high affinity with the Gli1 zinc finger domain that resulted from hydrogen-bonds to the THR243 and ASP216 amino acids residues. In addition, solasodine specifically bound with Gli1 and enhanced Gli1 protein stability in MCF7 cells. CONCLUSION: Here, our findings indicated that solasodine can directly suppresses Hh/Gli1 signaling, and is a novel anticancer candidate that targets CSCs.