TRAP1 regulates stemness through Wnt/β-catenin pathway in human colorectal carcinoma

Colorectal carcinoma (CRC) is a common cause of cancer-related death worldwide. Indeed, treatment failures are triggered by cancer stem cells (CSCs) that give rise to tumor repopulation upon initial remission. Thus, the role of the heat shock protein TRAP1 in stemness was investigated in CRC cell lines and human specimens, based on its involvement in colorectal carcinogenesis, through regulation of apoptosis, protein homeostasis and bioenergetics. Strikingly, co-expression between TRAP1 and stem cell markers was observed in stem cells located at the bottom of intestinal crypts and in CSCs sorted from CRC cell lines. Noteworthy, TRAP1 knockdown reduced the expression of stem cell markers and impaired colony formation, being the CSC phenotype and the anchorage-independent growth conserved in TRAP1-rich cancer cells. Consistently, the gene expression profiling of HCT116 cells showed that TRAP1 silencing results in the loss of the stem-like signature with acquisition of a more-differentiated phenotype and the downregulation of genes encoding for activating ligands and target proteins of Wnt/β-catenin pathway. Mechanistically, TRAP1 maintenance of stemness is mediated by the regulation of Wnt/β-catenin signaling, through the modulation of the expression of frizzled receptor ligands and the control of β-catenin ubiquitination/phosphorylation. Remarkably, TRAP1 is associated with higher expression of β-catenin and several Wnt/β-catenin target genes in human CRCs, thus supporting the relevance of TRAP1 regulation of β-catenin in human pathology. This study is the first demonstration that TRAP1 regulates stemness and Wnt/β-catenin pathway in CRC and provides novel landmarks in cancer biology and therapeutics

Development and characterization of phytosterol-enriched oil microcapsules for foodstuff application

Phytosterols are lipophilic compounds contained in plants and have several biological activities. The use of phytosterols in food fortification is hampered due to their high melting temperature, chalky taste, and low solubility in an aqueous system. Also, phytosterols are easily oxidized and are poorly absorbed by the human body. Formulation engineering coupled with microencapsulation could be used to overcome these problems. The aim of this study was to investigate the feasibility of encapsulating soybean oil enriched with phytosterols by spray-drying using ternary mixtures of health-promoting ingredients, whey protein isolate (WPI), inulin, and chitosan as carrier agents. The effect of different formulations and spray-drying conditions on the microencapsules properties, encapsulation efficiency, surface oil content, and oxidation stability were studied. It was found that spherical WPI-inulin-chitosan phytosterol-enriched soybean oil microcapsules with an average size below 50 μm could be produced with good encapsulation efficiency (85%), acceptable level of surface oil (11%), and water activity (0.2–0.4) that meet industrial requirements. However, the microcapsules showed very low oxidation stability with peroxide values reaching 101.7 meq O2/kg of oil just after production, and further investigations and optimization are required before any industrial application of this encapsulated system