Curcumin promotes cell cycle arrest and apoptosis of acute myeloid leukemia cells by inactivating AKT.
Oncol Rep
; 45(4)2021 04.
Article
em En
| MEDLINE
| ID: mdl-33649826
Curcumin, a phytochemical from rhizomes of the plant Curcuma longa, has been reported to exert potential anticancer properties in various cancer types, including acute myeloid leukemia (AML). However, the underlying mechanism remains poorly understood. The present study demonstrated that curcumin had a stronger cytotoxic activity against AML cells compared with three other types of phytochemicals (epigallocatechin gallate, genistein and resveratrol). Protein phosphorylation profiling using an antibody array identified that curcumin treatment increased the phosphorylation levels of 14 proteins and decreased those of four proteins. A proteinprotein interaction network was constructed using the STRING database, in which AKT was identified as a hub protein with the highest connectivity (PRAS40, 4EBP1, P70S6K, RAF1 and p27). Western blotting results indicated that curcumin dosedependently suppressed the phosphorylation of AKT, PRAS40, 4EBP1, P70S6K, RAF1 and p27 in AML cell lines (ML2 and OCIAML5). It was also demonstrated that curcumin regulated the cell cycle and apoptosisrelated proteins (cyclin D1, p21, Bcl2, cleavedcaspase3 and cleavedPARP), leading to cell cycle arrest and apoptosis in both ML2 and OCIAML5 cells. These effects of curcumin were enhanced by the AKT inhibitor afuresertib but were suppressed by the AKT activator SC79, indicating that curcumin functions via AKT. In the AML xenograft mouse model, curcumin and afuresertib synergistically suppressed the engraftment, proliferation and survival of AML cells. Collectively, the present study demonstrated that curcumin exerted antiAML roles by inactivating AKT and these findings may aid in the treatment of AML.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Leucemia Mieloide Aguda
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Curcumina
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Proteínas Proto-Oncogênicas c-akt
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article