Berberine Induces Autophagic Cell Death in Acute Lymphoblastic Leukemia by Inactivating AKT/mTORC1 Signaling.
Drug Des Devel Ther
; 14: 1813-1823, 2020.
Article
em En
| MEDLINE
| ID: mdl-32494123
ABSTRACT
INTRODUCTION:
Berberine has been reported to inhibit cancer cell growth by apoptosis induction and exhibits a protective role against cancer progression. The current study aims to investigate the effects of berberine on acute lymphoblastic leukemia (ALL) and the mechanism beyond apoptosis.METHODS:
Cell viability was determined in ALL cell lines EU-6 and SKW-3 using trypan blue staining. Cell autophagy was determined by immunofluorescence and Western blot. ALL xenograft mice were established to investigate the anti-tumor effects of BBR. The molecular mechanism was explored in ALL cell lines using siRNA and signaling inhibitors.RESULTS:
Herein, we show that berberine treatment significantly inhibits ALL cell viability and promotes cell death by inducing autophagy in a dose-dependent manner. Moreover, berberine significantly alleviates the aggressive pathological condition in ALL xenograft mice. Mechanistic studies exhibit that berberine induces autophagic death in ALL cells by inactivating AKT/mTORC1 signaling. Chemically targeting AKT/mTORC1 signaling controls berberine-induced cell autophagy in vitro, and blockade of autophagic process blunts berberine-alleviated pathological condition in vivo.DISCUSSION:
In conclusion, our study reveals that berberine could induce ALL cell autophagic death by inactivating AKT/mTORC1 signaling that could be used to develop small molecule drug for ALL treatment.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Berberina
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Proteínas Proto-Oncogênicas c-akt
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Leucemia-Linfoma Linfoblástico de Células Precursoras
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Alvo Mecanístico do Complexo 1 de Rapamicina
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Antineoplásicos
Tipo de estudo:
Diagnostic_studies
Limite:
Adolescent
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Adult
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Aged
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Child
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Child, preschool
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Humans
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Middle aged
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article