Curcumin potentiates the anti-leukemia effects of imatinib by downregulation of the AKT/mTOR pathway and BCR/ABL gene expression in Ph+ acute lymphoblastic leukemia.
Int J Biochem Cell Biol
; 65: 1-11, 2015 Aug.
Article
em En
| MEDLINE
| ID: mdl-25979368
ABSTRACT
Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is triggered by BCR/ABL and SRC family tyrosine kinases. They interact with each other and subsequently activate downstream growth-signaling pathways, including Raf/MEK/ERK, Akt/mTOR, and STAT5 pathways. Although imatinib is the standard treatment for Ph+ leukemia, response rate of Ph+ ALL to imatinib is low, relapse is frequent and quick. Studies have documented the potential anti-tumor activities of curcumin. However, whether curcumin can be used in the therapy for Ph+ ALL remains obscure. Here, we reported that curcumin induced apoptosis by inhibition of AKT/mTOR and ABL/STAT5 signaling, down-regulation of BCR/ABL expression, and induction of the BCL2/BAX imbalance. Curcumin exerted synergetic anti-leukemia effects with imatinib by inhibition of the imatinib-mediated overactivation of AKT/mTOR signaling and down-regulation of BCR/ABL gene expression. In primary samples from Ph+ ALL patients, curcumin inhibited cellular proliferation and down-regulated constitutive activation of growth-signaling pathways not only in newly diagnosed patients but also in imatinib-resistant patients. In Ph+ ALL mouse models, curcumin exhibited synergetic anti-leukemia effects with imatinib. These results demonstrated that curcumin might be a promising agent for Ph+ ALL patients.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
/
Tipos_de_cancer
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Leucemia
Base de dados:
MEDLINE
Assunto principal:
Leucemia Mielogênica Crônica BCR-ABL Positiva
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Protocolos de Quimioterapia Combinada Antineoplásica
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Curcumina
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Serina-Treonina Quinases TOR
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Mesilato de Imatinib
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Int J Biochem Cell Biol
Assunto da revista:
BIOQUIMICA
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
China