Daunorubicin induces GLI1dependent apoptosis in colorectal cancer cell lines.
Int J Oncol
; 64(6)2024 06.
Article
em En
| MEDLINE
| ID: mdl-38757343
ABSTRACT
Daunorubicin, also known as daunomycin, is a DNAtargeting anticancer drug that is used as chemotherapy, mainly for patients with leukemia. It has also been shown to have anticancer effects in monotherapy or combination therapy in solid tumors, but at present it has not been adequately studied in colorectal cancer (CRC). In the present study, from a screening using an FDAapproved drug library, it was found that daunorubicin suppresses GLIdependent luciferase reporter activity. Daunorubicin also increased p53 levels, which contributed to both GLI1 suppression and apoptosis. The current detailed investigation showed that daunorubicin promoted the ßTrCPmediated ubiquitination and proteasomal degradation of GLI1. Moreover, a competition experiment using BODIPYcyclopamine, a wellknown Smo inhibitor, suggested that daunorubicin does not bind to Smo in HCT116 cells. Administration of daunorubicin (2 mg/kg, ip, qod, 15 days) into HCT116 xenograft mice profoundly suppressed tumor progress and the GLI1 level in tumor tissues. Taken together, the present results revealed that daunorubicin suppresses canonical Hedgehog pathways in CRC. Ultimately, the present study discloses a new mechanism of daunorubicin's anticancer effect and might provide a rationale for expanding the clinical application of daunorubicin.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Colorretais
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Daunorrubicina
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Apoptose
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Proteína GLI1 em Dedos de Zinco
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article