Antiproliferative Activity of Stokesia laevis Ethanolic Extract in Combination with Several Food-Related Bioactive Compounds; In Vitro (Caco-2) and In Silico Docking (TNKS1 and TNKS2) Studies

Abstract

This study evaluates in vitro cytotoxic and antiproliferative activity on human colon tumor cell line Caco-2 (ATCC-HTB-37) of a standardized (5 mg GAE/mL) ethanolic extract from Stokesia laevis (Slae26), of five polyphenols compounds (reference substances, ref.), namely luteolin-7-O-glucoside, luteolin-8-C-glucoside, caffeic acid, gentisic acid, and p-aminobenzoic acid (PABA), as well as of Slae26 combinations with the five reference substances, 1:1 mass rate (GAE, ref.). Cell viability studies (MTS test) have revealed IC50 values of 36 μg GAE/mL in the case of Slae26 ethanolic extract, while Slae26 combinations with the five phenolics indicated IC50 values around 5 μg GAE/mL. In silico docking studies on the molecular targets human tankyrase 1 (TNKS1) and human tankyrase 2 (TNKS2) in complex with their native ligands, Co-crystallized 3J5A and Co-crystallized FLN, indicated score values of −104.15 and −76.97, respectively; in the series of the reference compounds studied, luteolin-7-O-glucoside was revealed with the best score values on both molecular targets (−80.49 and −85.17), together signifying real antiproliferative potential against human colon cancer of Slae26, of luteolin-7-O-glucoside, and of Slae26 combinations with all food-related bioactive compounds tested.

Phytochemical profiling, in vitro biological activities, and in silico (molecular docking and absorption, distribution, metabolism, excretion, toxicity) studies of Polygonum cognatum Meissn

“…Residues of TNKS 2 that interact with caffeic acid, gentisic acid, and flavone (standard ligand) were prominent in the interactions of TNKS 2 and the coumarin molecule (Figure 4B and Table 6) [25, 38]. In this study, it was observed that pi interactions were more dominant than hydrogen bond interactions.…”

“…In addition, Tyr-1071 (A), Ala-1062 (A), and Lys-1067 (A) residues and the flavone (ligand) were also found to be involved in pi interactions [38]. When the molecular docking studies of the caffeic acid and gentisic acid, are plant compounds, with TNKS 2 are examined, it was reported that caffeic acid formed hydrogen bonds with Ser-1068 (A) and Glu-1138 (C) residues like resveratrol [25]. Gentisic acid, which was examined in the same study, also made hydrogen bonds with Ser-1068 (A) residue in TNKS 2 [25].…”

“…When the molecular docking studies of the caffeic acid and gentisic acid, are plant compounds, with TNKS 2 are examined, it was reported that caffeic acid formed hydrogen bonds with Ser-1068 (A) and Glu-1138 (C) residues like resveratrol [25]. Gentisic acid, which was examined in the same study, also made hydrogen bonds with Ser-1068 (A) residue in TNKS 2 [25]. The binding affinity of resveratrol, which has a similar binding profile to the compounds in the literature, was calculated as −9.5 kcal/mol and the RMSD values were determined to be less than approximately 2 Å (Table 5 and Table S5).…”

“…The therapeutic effect of TNKS inhibition in various tumor models has been reported [31–33]. Therefore, the TNKS inhibitor potential of various small molecules has begun to be investigated [25]. In addition, DNA gyrase is associated with induction studies of bacterial death [34].…”

“…Therefore, the TNKS inhibitor potential of various small molecules has begun to be investigated [25]. In addition, DNA gyrase is associated with induction studies of bacterial death [34].…”