Eriocalyxin B induces apoptosis of t(8;21) leukemia cells through NF-κB and MAPK signaling pathways and triggers degradation of AML1-ETO oncoprotein in a caspase-3-dependent manner

Lan Wang, W. L. Zhao, J. S. Yan, P. Liu, H. P. Sun, G. B. Zhou, Z. Y. Weng, W. L. Wu, X. Q. Weng, X. J. Sun, Z. Chen, H. D. Sun, S. J. Chen

Research output: Contribution to journalArticle

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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-κB inactivation by preventing NF-κB nuclear translocation and inducing IκBα 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.

Original languageEnglish (US)
Pages (from-to)306-317
Number of pages12
JournalCell Death and Differentiation
Volume14
Issue number2
DOIs
StatePublished - Feb 2007
Externally publishedYes

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Oncogene Proteins
Caspase 3
Leukemia
Apoptosis
Diterpenes
Isodon
Down-Regulation
Lamiaceae
MAP Kinase Signaling System
Transcription Factor AP-1
Myeloid Cells
Hematopoietic Stem Cells
Heterografts
Acute Myeloid Leukemia
eriocalyxin B
Lymphoma
Phosphorylation
Cell Proliferation
Cell Line
Survival

ASJC Scopus subject areas

  • Cell Biology

Cite this

Eriocalyxin B induces apoptosis of t(8;21) leukemia cells through NF-κB and MAPK signaling pathways and triggers degradation of AML1-ETO oncoprotein in a caspase-3-dependent manner. / Wang, Lan; Zhao, W. L.; Yan, J. S.; Liu, P.; Sun, H. P.; Zhou, G. B.; Weng, Z. Y.; Wu, W. L.; Weng, X. Q.; Sun, X. J.; Chen, Z.; Sun, H. D.; Chen, S. J.

In: Cell Death and Differentiation, Vol. 14, No. 2, 02.2007, p. 306-317.

Research output: Contribution to journalArticle

Wang, Lan ; Zhao, W. L. ; Yan, J. S. ; Liu, P. ; Sun, H. P. ; Zhou, G. B. ; Weng, Z. Y. ; Wu, W. L. ; Weng, X. Q. ; Sun, X. J. ; Chen, Z. ; Sun, H. D. ; Chen, S. J. / Eriocalyxin B induces apoptosis of t(8;21) leukemia cells through NF-κB and MAPK signaling pathways and triggers degradation of AML1-ETO oncoprotein in a caspase-3-dependent manner. In: Cell Death and Differentiation. 2007 ; Vol. 14, No. 2. pp. 306-317.
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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-κB inactivation by preventing NF-κB nuclear translocation and inducing IκBα 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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