Potent Anticancer Activities of Beauvericin Against KB Cells In Vitro by Inhibiting the Expression of ACAT1 and Exploring Binding Affinity.
Anticancer Agents Med Chem
; 22(5): 897-904, 2022.
Article
em En
| MEDLINE
| ID: mdl-34353273
ABSTRACT
BACKGROUND AND OBJECTIVE:
Beauvericin (BEA), a cyclic hexadepsipeptide mycotoxin, is a potent inhibitor of the acyl-CoA cholesterol acyltransferase enzyme 1 (ACAT1), involved in multiple tumor-correlated pathways. However, the binding mechanisms between BEA and ACAT1 were not elucidated.METHODS:
BEA was purified from a mangrove entophytic Fusarium sp. KL11. Single-crystal X-ray diffraction was used to determine the structure of BEA. Wound healing assays of BEA against KB cell line and MDA-MB-231 cell line were evaluated. Inhibitory potency of BEA against ACAT1 was determined by ELISA assays. Molecular docking was carried out to illuminate the bonding mechanism between BEA and ACAT1.RESULTS:
The structure of BEA was confirmed by X-ray diffraction, indicating a monoclinic crystal system with P21 space group (α = 90°, ß = 92.2216(9)°, γ= 90°). BEA displayed migration-inhibitory activities against KB cells and MDA-MB-231 cells In Vitro. ELISA assays revealed that the protein expression level of ACAT1 in KB cells was significantly decreased after BEA treatment (P ï¼0.05). Molecular docking demonstrated that BEA formed hydrogen bond with His425 and pi-pi staking with Tyr429 in ACAT1.CONCLUSION:
BEA sufficiently inhibited the proliferation and migration of KB cells and MDA-MB-231 cells by downregulating ACAT1 expression. In addition, BEA potentially possessed a strong binding affinity with ACAT1. BEA may serve as a potential lead compound for the development of a new ACAT1-targeted anticancer drug.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Acetil-CoA C-Acetiltransferase
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Depsipeptídeos
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Micotoxinas
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article