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

Abstract

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

Heparin-Binding Protein 17/Fibroblast Growth Factor-Binding Protein-1 Knockout Inhibits Proliferation and Induces Differentiation of Squamous Cell Carcinoma Cells

“…When we constructed PPI networks of molecules elevated by cDNA microarray and proteomic analysis, both networks were similar ( Supplementary Figures S1 and S2 ). Although there are many reports on the induction of cancer cell differentiation and growth inhibition [ 47 , 48 ], there are almost no reports on the involvement of HBp17. It was reported that FLG expression increases in HBp17 -KO mice [ 49 ].…”

Growth Inhibition and Apoptotic Effect of Pine Extract and Abietic Acid on MCF-7 Breast Cancer Cells via Alteration of Multiple Gene Expressions Using In Vitro Approach

“…The developed color, due to soluble formazan, was read at 570 nm with a microplate reader (800TSUV Biotek ELISA Reader, Agilent, Santa Clara, CA, USA), and corresponding optical densities were used for calculation of IC 50 . The corresponding selectivity index was calculated based on IC 50 values of the pine extract and abietic acid on both noncancerous and cancerous cells according to Equation (1) [ 24 , 91 ]: SI = IC 50 (non-cancerous cells)/IC 50 (cancerous cells) …”

Retinoic Acid-Induced 2 (RAI2) Is a Novel Antagonist of Wnt/β-Catenin Signaling Pathway and Potential Biomarker of Chemosensitivity in Colorectal Cancer

“…Abdelaal MR. et al. reported that EC-synthetic retinoids can be effective, alone or in combinations, for a potential anticancer activity to colorectal cancer, with overexpression of E-cadherin, RAI2, and Werner (WRN) genes ( 39 ). Both 5-Aza-2′-deoxycytidine (DAC, a demethylation agent) and retinoic acid could induce the expression of RAI2 in colorectal cancer, which was proved in our previous ( 24 ) and supplementary data of this study.…”