PRMT1 inhibition induces differentiation of colon cancer cells.
Sci Rep
; 10(1): 20030, 2020 11 18.
Article
em En
| MEDLINE
| ID: mdl-33208761
ABSTRACT
Differentiation therapy has been recently revisited as a prospective approach in cancer therapy by targeting the aberrant growth, and repairing the differentiation and cell death programs of cancer cells. However, differentiation therapy of solid tumors is a challenging issue and progress in this field is limited. We performed High Throughput Screening (HTS) using a novel dual multiplex assay to discover compounds, which induce differentiation of human colon cancer cells. Here we show that the protein arginine methyl transferase (PRMT) type 1 inhibitor, MS023, is a potent inducer of colon cancer cell differentiation with a large therapeutic window. Differentiation changes in the highly aggressive human colon cancer cell line (HT-29) were proved by proteomic and genomic approaches. Growth of HT-29 xenograft in nude mice was significantly delayed upon MS023 treatment and immunohistochemistry of tumor indicated differentiation changes. These findings may lead to development of clinically effective anti-cancer drugs based on the mechanism of cancer cell differentiation.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteína-Arginina N-Metiltransferases
/
Proteínas Repressoras
/
Biomarcadores Tumorais
/
Regulação Neoplásica da Expressão Gênica
/
Diferenciação Celular
/
Neoplasias do Colo
/
Antineoplásicos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Sci Rep
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Israel