Tetra-O-methyl nordihydroguaiaretic acid inhibits growth and induces death of leukemia cells independent of Cdc2 and survivin

Duncan H. Mak; Wendy D. Schober; Wenjing Chen; Jonathan Heller; Michael Andreeff; Bing Z. Carter

doi:10.1080/10428190601186143

Tetra-O-methyl nordihydroguaiaretic acid inhibits growth and induces death of leukemia cells independent of Cdc2 and survivin

Duncan H. Mak, Wendy D. Schober, Wenjing Chen, Jonathan Heller, Michael Andreeff, Bing Z. Carter

Leukemia

Research output: Contribution to journal › Article › peer-review

16 Scopus citations

Abstract

Tetra-O-methyl nordihydroguaiaretic acid (M4N) was shown to induce G2 arrest and suppress human xenograft tumor growth by inhibiting Cdc2 and survivin. We examined the effect of M4N on leukemia and found that M4N inhibited growth and induced cell death in leukemic cell lines and blasts from AML patients. However, no significant changes in Cdc2 and survivin levels and G2 arrest were observed. Cell death and growth inhibition were dependent neither on XIAP, Bcl-2, and Bcl-X_L levels nor on caspase-8. M4N did not promote cell differentiation in HL-60 cells. Interestingly, significant inhibition of AKT phosphorylation was observed in M4N treated OCI-AML3 cells. Collectively, our data showed that M4N inhibited cell growth and induced cell death in both leukemic cell lines and AML patient sample via a mechanism not mediated by Cdc2 and survivin inhibition and suggested that the extrinsic and the mitochondrial apoptotic pathways are not essential.

Original language	English (US)
Pages (from-to)	774-785
Number of pages	12
Journal	Leukemia and Lymphoma
Volume	48
Issue number	4
DOIs	https://doi.org/10.1080/10428190601186143
State	Published - Apr 2007

Keywords

Cdc2
Survivin
Tetra-O-methyl nordihydroguaiaretic acid

ASJC Scopus subject areas

Hematology
Oncology
Cancer Research

MD Anderson CCSG core facilities

Flow Cytometry and Cellular Imaging Facility

Access to Document

10.1080/10428190601186143

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title = "Tetra-O-methyl nordihydroguaiaretic acid inhibits growth and induces death of leukemia cells independent of Cdc2 and survivin",

abstract = "Tetra-O-methyl nordihydroguaiaretic acid (M4N) was shown to induce G2 arrest and suppress human xenograft tumor growth by inhibiting Cdc2 and survivin. We examined the effect of M4N on leukemia and found that M4N inhibited growth and induced cell death in leukemic cell lines and blasts from AML patients. However, no significant changes in Cdc2 and survivin levels and G2 arrest were observed. Cell death and growth inhibition were dependent neither on XIAP, Bcl-2, and Bcl-XL levels nor on caspase-8. M4N did not promote cell differentiation in HL-60 cells. Interestingly, significant inhibition of AKT phosphorylation was observed in M4N treated OCI-AML3 cells. Collectively, our data showed that M4N inhibited cell growth and induced cell death in both leukemic cell lines and AML patient sample via a mechanism not mediated by Cdc2 and survivin inhibition and suggested that the extrinsic and the mitochondrial apoptotic pathways are not essential.",

keywords = "Cdc2, Survivin, Tetra-O-methyl nordihydroguaiaretic acid",

author = "Mak, {Duncan H.} and Schober, {Wendy D.} and Wenjing Chen and Jonathan Heller and Michael Andreeff and Carter, {Bing Z.}",

note = "Funding Information: This work is supported in part by grants from the National Institutes of Health (PO1 CA49639, PO1 CA55164, and CA16672) to M.A. and from Erimos Pharmaceuticals to B.Z.C. We thank Rosemarie Lauzon and Elena Vess for assistance in the preparation of the manuscript.",

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pages = "774--785",

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T1 - Tetra-O-methyl nordihydroguaiaretic acid inhibits growth and induces death of leukemia cells independent of Cdc2 and survivin

AU - Mak, Duncan H.

AU - Schober, Wendy D.

AU - Chen, Wenjing

AU - Heller, Jonathan

AU - Andreeff, Michael

AU - Carter, Bing Z.

N1 - Funding Information: This work is supported in part by grants from the National Institutes of Health (PO1 CA49639, PO1 CA55164, and CA16672) to M.A. and from Erimos Pharmaceuticals to B.Z.C. We thank Rosemarie Lauzon and Elena Vess for assistance in the preparation of the manuscript.

PY - 2007/4

Y1 - 2007/4

N2 - Tetra-O-methyl nordihydroguaiaretic acid (M4N) was shown to induce G2 arrest and suppress human xenograft tumor growth by inhibiting Cdc2 and survivin. We examined the effect of M4N on leukemia and found that M4N inhibited growth and induced cell death in leukemic cell lines and blasts from AML patients. However, no significant changes in Cdc2 and survivin levels and G2 arrest were observed. Cell death and growth inhibition were dependent neither on XIAP, Bcl-2, and Bcl-XL levels nor on caspase-8. M4N did not promote cell differentiation in HL-60 cells. Interestingly, significant inhibition of AKT phosphorylation was observed in M4N treated OCI-AML3 cells. Collectively, our data showed that M4N inhibited cell growth and induced cell death in both leukemic cell lines and AML patient sample via a mechanism not mediated by Cdc2 and survivin inhibition and suggested that the extrinsic and the mitochondrial apoptotic pathways are not essential.

AB - Tetra-O-methyl nordihydroguaiaretic acid (M4N) was shown to induce G2 arrest and suppress human xenograft tumor growth by inhibiting Cdc2 and survivin. We examined the effect of M4N on leukemia and found that M4N inhibited growth and induced cell death in leukemic cell lines and blasts from AML patients. However, no significant changes in Cdc2 and survivin levels and G2 arrest were observed. Cell death and growth inhibition were dependent neither on XIAP, Bcl-2, and Bcl-XL levels nor on caspase-8. M4N did not promote cell differentiation in HL-60 cells. Interestingly, significant inhibition of AKT phosphorylation was observed in M4N treated OCI-AML3 cells. Collectively, our data showed that M4N inhibited cell growth and induced cell death in both leukemic cell lines and AML patient sample via a mechanism not mediated by Cdc2 and survivin inhibition and suggested that the extrinsic and the mitochondrial apoptotic pathways are not essential.

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Tetra-O-methyl nordihydroguaiaretic acid inhibits growth and induces death of leukemia cells independent of Cdc2 and survivin

Abstract

Keywords

ASJC Scopus subject areas

MD Anderson CCSG core facilities

Access to Document

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