Revealing the Potential Application of EC-Synthetic Retinoid Analogues in Anticancer Therapy.

摘要: (1) Background and Aim: All-trans retinoic acid (ATRA) induces differentiation inhibits growth of many cancer cells. However, resistance develops rapidly prompting the urgent need for new synthetic potent derivatives. EC19 EC23 are two retinoids with stem cell neuro-differentiation activity. Here, these compounds were screened their in vitro antiproliferative cytotoxic activity using an array different lines. (2) Methods: MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, AV/PI (annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI)), cycle analysis, immunocytochemistry, gene expression Western blotting, measurement glutamate total antioxidant concentrations recruited. (3) Results: HepG2, Caco-2, MCF-7 most sensitive lines; HepG2 (ATRA; 36.2, EC19; 42.2 EC23; 0.74 µM), Caco-2 58.0, 10.8 14.7 µM) 99.0, 9.4 5.56 µM). cells selected further biochemical investigations. Isobologram analysis revealed combined synergistic effects 5-fluorouracil substantial reduction IC50. All induced apoptosis but had higher potency, significant arrest at subG0-G1, -S G2/M phases, than ATRA EC23. Moreover, reduced cellular metastasis a transwell invasion assay due to overexpression E-cadherin, acid-induced 2 (RAI2) Werner (WRN) genes. (4) Conclusion: The present study suggests that EC-synthetic retinoids, particularly EC19, can be effective, alone or combinations, potential anticancer colorectal cancer. Further vivo studies recommended pave way clinical applications.