Enantioselective toxicity effect and mechanism of hexaconazole enantiomers to human breast cancer cells.
Food Chem Toxicol
; 173: 113612, 2023 Mar.
Article
en En
| MEDLINE
| ID: mdl-36681264
ABSTRACT
The toxicity effects of chiral pesticides on living organisms have attracted an increasing public attention. This study aims to investigate the toxicity effect and mechanism of hexaconazole (HEX) to human breast cancer cell (MCF-7) at enantiomer levels. HEX exposure obviously inhibited cells activities in a dose-dependent manner. Under the conditions of VIP >1 and p < 0.05, a total of 255 and 177 differential metabolites (DMs), 17 and 15 amino acid- and lipid-related metabolic pathways were disturbed after (+)-HEX and (-)-HEX exposure, respectively. HEX exposure may affect cell membrane function, signal transduction, and cell differentiation. We further investigated the mechanism of enantioselective differences by using molecular docking which showed that CYP17A1 was the main enzyme that leading to endocrine disrupting effects with the binding energy of -6.30 and -6.08 kcal/mol compared to CYP19A1 enzyme which were -5.81 and -5.93 kcal/mol for (+)-HEX and (-)-HEX, respectively. The docking results explained the reasons why (+)-HEX achieved higher cytotoxicity and induced more seriously metabolic profiles than its antipode. These findings could provide a new insight to understand the enantioselective cytotoxicity effect and mechanism of HEX and will be conducive to assessing its risk to human health at enantiomer levels.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Plaguicidas
/
Neoplasias de la Mama
Límite:
Female
/
Humans
Idioma:
En
Revista:
Food Chem Toxicol
Año:
2023
Tipo del documento:
Article
País de afiliación:
China