Spironolactone inhibits the growth of cancer stem cells by impairing DNA damage response.
Oncogene
; 38(17): 3103-3118, 2019 04.
Article
em En
| MEDLINE
| ID: mdl-30622338
ABSTRACT
The cancer stem cell (CSC) model suggests that a subpopulation of cells within the tumor, the CSCs, is responsible for cancer relapse and metastasis formation. CSCs hold unique characteristics, such as self-renewal, differentiation abilities, and resistance to chemotherapy, raising the need for discovering drugs that target CSCs. Previously we have found that the antihypertensive drug spironolactone impairs DNA damage response in cancer cells. Here we show that spironolactone, apart from inhibiting cancerous cell growth, is also highly toxic to CSCs. Notably, we demonstrate that CSCs have high basal levels of DNA double-strand breaks (DSBs). Mechanistically, we reveal that spironolactone does not damage the DNA but impairs DSB repair and induces apoptosis in cancer cells and CSCs while sparing healthy cells. In vivo, spironolactone treatment reduced the size and CSC content of tumors. Overall, we suggest spironolactone as an anticancer reagent, toxic to both cancer cells and, particularly to, CSCs.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Espironolactona
/
Células-Tronco Neoplásicas
/
Reparo do DNA
/
Neoplasias
/
Antineoplásicos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Oncogene
Assunto da revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Israel