Sanguinarine targets BRD4 to suppress cell proliferation and migration in clear cell renal cell carcinoma.
J Biochem Mol Toxicol
; 37(11): e23451, 2023 Nov.
Article
em En
| MEDLINE
| ID: mdl-37393519
ABSTRACT
Sanguinarine is an alkaloid with diverse biological activities, nevertheless, whether it can target epigenetic modifiers remains unknown. In this study, sanguinarine was characterized as a strong BRD4 inhibitor with IC50 = 361.3 nM against BRD4 (BD1) and IC50 = 302.7 nM against BRD4 (BD2) that can inactivate BRD4 reversibly. Additional cellular assays suggested that sanguinarine can bind BRD4 in human clear cell renal cell carcinoma (ccRCC) cell line 786-O and inhibit cell growth with IC50 (24 h) = 0.6752 µM and IC50 (48 h) = 0.5959 µM in a BRD4 dependent manner partially. Meanwhile, sanguinarine can inhibit the migration of 786-O cells in vitro and in vivo, and reverse epithelial-mesenchymal transition. Moreover, it can inhibit 786-O cells proliferation in vivo in a BRD4 dependent manner partially. In sum, our study identified BRD4 as a new target of sanguinarine, and sanguinarine may serve as a potential therapeutic agent against ccRCC.
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Base de dados:
MEDLINE
Assunto principal:
Carcinoma de Células Renais
/
Neoplasias Renais
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China