Journal
CELL DEATH AND DIFFERENTIATION
Volume 14, Issue 2, Pages 306-317Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.cdd.4401996
Keywords
eriocalyxin B; acute myeloid leukemia; apoptosis; NF-kappa B; MAPK; AML1-ETO
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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-X-L 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-kappa B inactivation by preventing NF-kappa B nuclear translocation and inducing I kappa B alpha 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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