Berberine Induces Autophagic Cell Death in Acute Lymphoblastic Leukemia by Inactivating AKT/mTORC1 Signaling.
Drug Des Devel Ther
; 14: 1813-1823, 2020.
Article
in 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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Berberine
/
Proto-Oncogene Proteins c-akt
/
Precursor Cell Lymphoblastic Leukemia-Lymphoma
/
Mechanistic Target of Rapamycin Complex 1
/
Antineoplastic Agents
Type of study:
Diagnostic_studies
Limits:
Adolescent
/
Adult
/
Aged
/
Child
/
Child, preschool
/
Humans
/
Middle aged
Language:
En
Journal:
Drug Des Devel Ther
Journal subject:
FARMACOLOGIA
/
TERAPIA POR MEDICAMENTOS
Year:
2020
Document type:
Article