Anti-Proliferative Potential of Cynaroside and Orientin—In Silico (DYRK2) and In Vitro (U87 and Caco-2) Studies

Abstract

Luteolin derivates are plant compounds with multiple benefits for human health. Stability to heat and acid hydrolysis and high resistance to (auto)oxidation are other arguments for the laden interest in luteolin derivates today. The present study was designed to compare the in silico and in vitro anti-proliferative potential of two luteolin derivates, luteolin-7-O-glucoside/cynaroside (7-Lut) and luteolin-8-C-glucoside/orientin (8-Lut). In silico investigations were carried out on the molecular target, namely, the human dual specificity tyrosine phosphorylation-regulated kinase 2 (DYRK2) in association with its natural ligand, curcumin (PDB ID: 5ZTN), by CLC Drug Discovery Workbench v. 1.5.1. software and Molegro Virtual Docker (MVD) v. MVD 2019.7.0. software. In vitro studies were performed on two human tumor cell lines, glioblastoma (U87) and colon carcinoma (Caco-2), respectively. Altogether, docking studies have revealed 7-Lut and 8-Lut as effective inhibitors of DYRK2, even stronger than the native ligand curcumin; in vitro studies indicated the ability of both luteolin glucosides to inhibit the viability of both human tumor cell lines, up to 85% at 50 and 100 µg/mL, respectively; the most augmented cytotoxic and anti-proliferative effects were obtained for U87 exposed to 7-Lut (IC50 = 26.34 µg/mL). The results support further studies on cynaroside and orientin to create drug formulas targeting glioblastoma and colon carcinoma in humans.

Linking Variability in Phytochemical Composition with Safety Profile of Thymus carnosus Boiss. Extracts: Effect of Major Compounds and Evaluation of Markers of Oxidative Stress and Cell Death

“…Regarding the flavonoids tested, one study indicated that exposing Caco-2 cells to L-7-G, for 48 h, significantly reduces cell viability to 50% of control, at ~55 µM [27], a value much lower than the one here presented (Figure 2C). Another study reported a 38% reduction in the viability of Caco-2 cells exposed for 24 h to 223 µM L-7-G [28], a value similar to that presented in Figure 2C. L-7-G was shown to reduce HepG2 cells' viability to ~50% at 44.60 µM [29], a value also lower than the one here reported (Figure 2K).…”