Eriocalyxin B induces apoptosis of t(8;21) leukemia cells through NF-kappaB and MAPK signaling pathways and triggers degradation of AML1-ETO oncoprotein in a caspase-3-dependent manner.
Cell Death Differ
; 14(2): 306-17, 2007 Feb.
Article
en En
| MEDLINE
| ID: mdl-16778832
ABSTRACT
Diterpenoids isolated from Labiatae family herbs have strong antitumor activities with low toxicity. In this study, Eriocalyxin B (EriB), a diterpenoid extracted from Isodon eriocalyx, was tested on human leukemia/lymphoma cells and murine leukemia models. Acute myeloid leukemia cell line Kasumi-1 was most sensitive to EriB. Significant apoptosis was observed, concomitant with Bcl-2/Bcl-XL downregulation, mitochondrial instability and caspase-3 activation. AML1-ETO oncoprotein was degraded in parallel to caspase-3 activation. EriB-mediated apoptosis was associated with NF-kappaB inactivation by preventing NF-kappaB nuclear translocation and inducing IkappaBalpha cleavage, and disturbance of MAPK pathway by downregulating ERK1/2 phosphorylation and activating AP-1. Without affecting normal hematopoietic progenitor cells proliferation, EriB was effective on primary t(8;21) leukemia blasts and caused AML1-ETO degradation. In murine t(8;21) leukemia models, EriB remarkably prolonged the survival time or decreased the xenograft tumor size. Together, EriB might be a potential treatment for t(8;21) leukemia by targeting AML1-ETO oncoprotein and activating apoptosis pathways.
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Banco de datos:
MEDLINE
Asunto principal:
Leucemia Mieloide Aguda
/
Proteínas de Fusión Oncogénica
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FN-kappa B
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Apoptosis
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Sistema de Señalización de MAP Quinasas
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Diterpenos
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Subunidad alfa 2 del Factor de Unión al Sitio Principal
/
Caspasa 3
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Death Differ
Año:
2007
Tipo del documento:
Article
País de afiliación:
China