CDDO-imidazolide mediated inhibition of malignant cell growth in Waldenström macroglobulinemia

Sherine F. Elsawa; Anne J. Novak; Deanna Grote; Marina Konopleva; Michael Andreeff; Thomas E. Witzig; Stephen M. Ansell

doi:10.1016/j.leukres.2008.03.033

CDDO-imidazolide mediated inhibition of malignant cell growth in Waldenström macroglobulinemia

Sherine F. Elsawa, Anne J. Novak, Deanna Grote, Marina Konopleva, Michael Andreeff, Thomas E. Witzig, Stephen M. Ansell

Hematology

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

7 Scopus citations

Abstract

Waldenström macroglobulinemia (WM) is a B-cell malignancy that remains incurable. Synthetic triterpenoids (ST), 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO), its methyl ester derivative (CDDO-Me) and imidazolide derivative (CDDO-Im) induce cell death and inhibit growth of various malignancies and hold promise as treatment for cancer patients. We examined the therapeutic potential of these compounds in WM. All three forms of CDDO induced equal toxicity in BCWM.1 cells. In malignant B cells from WM patients, CDDO-Im induced the greatest toxicity. CDDO-Im inhibited proliferation at nanomolar concentrations and arrested the cells in G0/G1. CDDO-Im induced apoptotic cell death that was partially abolished in the presence of caspase inhibitor. CDDO-Im also inhibited survival pathways that have been shown to be important in WM. Overall, our data suggest that ST are likely to provide therapeutic efficacy for WM patients.

Original language	English (US)
Pages (from-to)	1895-1902
Number of pages	8
Journal	Leukemia Research
Volume	32
Issue number	12
DOIs	https://doi.org/10.1016/j.leukres.2008.03.033
State	Published - Dec 2008

Keywords

CDDO
CDDO-Im
Non-Hodgkin lymphoma
Therapy
Waldenström macroglobulinemia

ASJC Scopus subject areas

Hematology
Oncology
Cancer Research

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10.1016/j.leukres.2008.03.033

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@article{f13b19be02c84c0f9e1810231a14e850,

title = "CDDO-imidazolide mediated inhibition of malignant cell growth in Waldenstr{\"o}m macroglobulinemia",

abstract = "Waldenstr{\"o}m macroglobulinemia (WM) is a B-cell malignancy that remains incurable. Synthetic triterpenoids (ST), 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO), its methyl ester derivative (CDDO-Me) and imidazolide derivative (CDDO-Im) induce cell death and inhibit growth of various malignancies and hold promise as treatment for cancer patients. We examined the therapeutic potential of these compounds in WM. All three forms of CDDO induced equal toxicity in BCWM.1 cells. In malignant B cells from WM patients, CDDO-Im induced the greatest toxicity. CDDO-Im inhibited proliferation at nanomolar concentrations and arrested the cells in G0/G1. CDDO-Im induced apoptotic cell death that was partially abolished in the presence of caspase inhibitor. CDDO-Im also inhibited survival pathways that have been shown to be important in WM. Overall, our data suggest that ST are likely to provide therapeutic efficacy for WM patients.",

keywords = "CDDO, CDDO-Im, Non-Hodgkin lymphoma, Therapy, Waldenstr{\"o}m macroglobulinemia",

author = "Elsawa, {Sherine F.} and Novak, {Anne J.} and Deanna Grote and Marina Konopleva and Michael Andreeff and Witzig, {Thomas E.} and Ansell, {Stephen M.}",

note = "Funding Information: Supported in part by grant CA97274 from the National Institute of Health (SMA), a grant from the International Waldenstr{\"o}m's Macroglobulinemia Foundation (SMA) and grant CA16672 from the National Cancer Institute (MA). SFE was supported in part by T32 HL67742 from the National Institute of Health. ",

year = "2008",

month = dec,

doi = "10.1016/j.leukres.2008.03.033",

language = "English (US)",

volume = "32",

pages = "1895--1902",

journal = "Leukemia Research",

issn = "0145-2126",

publisher = "Elsevier Limited",

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TY - JOUR

T1 - CDDO-imidazolide mediated inhibition of malignant cell growth in Waldenström macroglobulinemia

AU - Elsawa, Sherine F.

AU - Novak, Anne J.

AU - Grote, Deanna

AU - Konopleva, Marina

AU - Andreeff, Michael

AU - Witzig, Thomas E.

AU - Ansell, Stephen M.

N1 - Funding Information: Supported in part by grant CA97274 from the National Institute of Health (SMA), a grant from the International Waldenström's Macroglobulinemia Foundation (SMA) and grant CA16672 from the National Cancer Institute (MA). SFE was supported in part by T32 HL67742 from the National Institute of Health.

PY - 2008/12

Y1 - 2008/12

N2 - Waldenström macroglobulinemia (WM) is a B-cell malignancy that remains incurable. Synthetic triterpenoids (ST), 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO), its methyl ester derivative (CDDO-Me) and imidazolide derivative (CDDO-Im) induce cell death and inhibit growth of various malignancies and hold promise as treatment for cancer patients. We examined the therapeutic potential of these compounds in WM. All three forms of CDDO induced equal toxicity in BCWM.1 cells. In malignant B cells from WM patients, CDDO-Im induced the greatest toxicity. CDDO-Im inhibited proliferation at nanomolar concentrations and arrested the cells in G0/G1. CDDO-Im induced apoptotic cell death that was partially abolished in the presence of caspase inhibitor. CDDO-Im also inhibited survival pathways that have been shown to be important in WM. Overall, our data suggest that ST are likely to provide therapeutic efficacy for WM patients.

AB - Waldenström macroglobulinemia (WM) is a B-cell malignancy that remains incurable. Synthetic triterpenoids (ST), 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO), its methyl ester derivative (CDDO-Me) and imidazolide derivative (CDDO-Im) induce cell death and inhibit growth of various malignancies and hold promise as treatment for cancer patients. We examined the therapeutic potential of these compounds in WM. All three forms of CDDO induced equal toxicity in BCWM.1 cells. In malignant B cells from WM patients, CDDO-Im induced the greatest toxicity. CDDO-Im inhibited proliferation at nanomolar concentrations and arrested the cells in G0/G1. CDDO-Im induced apoptotic cell death that was partially abolished in the presence of caspase inhibitor. CDDO-Im also inhibited survival pathways that have been shown to be important in WM. Overall, our data suggest that ST are likely to provide therapeutic efficacy for WM patients.

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KW - Therapy

KW - Waldenström macroglobulinemia

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CDDO-imidazolide mediated inhibition of malignant cell growth in Waldenström macroglobulinemia

Abstract

Keywords

ASJC Scopus subject areas

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