Inhibitory activities of 20(R, S)-protopanaxatriol against epidermal growth factor receptor tyrosine kinase.
Food Chem Toxicol
; 155: 112411, 2021 Sep.
Article
en En
| MEDLINE
| ID: mdl-34271119
ABSTRACT
As major metabolites of protopanaxatriol-type ginsenosides, 20(R, S)-protopanaxatriol [20(R, S)-PPT] display multiple bioactivities. This work aimed to investigate the inhibitory activities of 20(R, S)-PPT against epidermal growth factor receptor tyrosine kinase and the potential mechanism. 20(R, S)-PPT inhibited the proliferation of HepG2 cells in a dose-dependent manner and blocked cell cycle progression at G1/G0 phase. Then 20(R, S)-PPT were found to influence the protein expressions involved in epidermal growth factor receptor (EGFR)-mitogen-activated protein kinase (MAPK) signaling pathway. Molecular docking suggested that 20(R, S)-PPT could bind to the active sites of all target proteins in EGFR-MAPK pathway. It is worth noting that 20(R, S)-PPT showed stronger binding capacities with EGFR, compared with other proteins. Hence, this work further investigated the binding interactions and binding stabilities between 20(R, S)-PPT and EGFR. Both hydrophobic interactions and hydrogen bonds contributed to the 20(R, S)-PPT-EGFR binding. In addition, the in vitro inhibitory activities of 20(R, S)-PPT against EGFR tyrosine kinase were observed in a homogeneous time-resolved fluorescence assay, with the IC50 values of 24.10 ± 0.17 and 33.19 ± 0.19 µM respectively. Taken together with the above results, both of 20(R)-PPT and 20(S)-PPT might serve as potential EGFR tyrosine kinase inhibitors.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Sapogeninas
/
Inhibidores de Proteínas Quinasas
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Receptores ErbB
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Antineoplásicos
Límite:
Humans
Idioma:
En
Revista:
Food Chem Toxicol
Año:
2021
Tipo del documento:
Article
País de afiliación:
China