3 research outputs found

    Bax/Tubulin/Epithelial-Mesenchymal Pathways Determine the Efficacy of Silybin Analog HM015k in Colorectal Cancer Cell Growth and Metastasis

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    The inhibition of apoptosis, disruption of cellular microtubule dynamics, and over-activation of the epithelial mesenchymal transition (EMT), are involved in the progression, metastasis, and resistance of colorectal cancer (CRC) to chemotherapy. Therefore, the design of a molecule that can target these pathways could be an effective strategy to reverse CRC progression and metastasis. In this study, twelve novel silybin derivatives, HM015a-HM015k (15a−15k) and compound 17, were screened for cytotoxicity in CRC cell lines. Compounds HM015j and HM015k (15k and 15j) significantly decreased cell proliferation, inhibited colony formation, and produced cell cycle arrest in CRC cells. Furthermore, 15k significantly induced the formation of reactive oxygen species and apoptosis. It induced the cleavage of the intrinsic apoptotic protein (Bax p21) to its more efficacious fragment, p18. Compound 15k also inhibited tubulin expression and disrupted its structure. Compound 15k significantly decreased metastatic LOVO cell migration and invasion. Furthermore, 15k reversed mesenchymal morphology in HCT116 and LOVO cells. Additionally, 15k significantly inhibited the expression of the mesenchymal marker N-cadherin and upregulated the expression of the epithelial marker, E-cadherin. Compound 15k inhibited the expression of key proteins known to induce EMT (i.e., DVL3, β-catenin, c-Myc) and upregulated the anti-metastatic protein, cyclin B1. Overall, in vitro, 15k significantly inhibited CRC progression and metastasis by inhibiting apoptosis, tubulin activity and the EMT pathways. Overall, these data suggest that compound 15k should be tested in vivo in a CRC animal model for further development

    A green/sustainable organocatalytic pathway for the preparation of esterified supercritical CO2-dried potato starch products

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    Production of renewable and modified starch-based products was achieved using a sustainable catalyst and an environmentally friendly drying process via supercritical CO2. Potato starch was modified via a sustainable and green esterification process with acetic anhydride reagent implementing a novel organocatalytic pathway at different periods of time (0.5, 3 and 7 h) by applying an esterification reaction at 120°C targeting intermediate degrees of substitution (i.e., 0.2 < DS <1.5) finding potential applications as polymer packaging materials. The final modified samples were divided into two fractions, where the first fraction was dried under vacuum at 80° C for 24 h and the second fraction was dried under supercritical CO2 at 40° C and 100 bars for 2 h. The final products were analyzed using an array of characterization techniques such as Fourier transform infrared (FTIR), Proton nuclear magnetic resonance (1H-NMR), scanning electron microscopy (SEM), X-ray diffraction (XRD), N2 physisorption, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and Karl Fischer. The chemical structure of both fractions was similar as confirmed by the different characterization techniques. Drying under supercritical CO2 preserved some pores in the modified starch materials as opposed to thermal oven drying, as was confirmed by N2 physisorption measurements. The degree of substitution (DS) was determined using three different techniques; titration, high performance liquid chromatography (HPLC) and solution state proton nuclear magnetic resonance (1H NMR) spectroscopy and the values were greater than 0.2 and less than 1.5 indicating intermediate degrees of substitution
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