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[Cancer Research 59, 336-341, January 1, 1999]
© 1999 American Association for Cancer Research
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[Cancer Research 59, 336-341, January 15, 1999]
© 1999 American Association for Cancer Research

Advances in Brief

A Novel Synthetic Oleanane Triterpenoid, 2-Cyano-3,12-dioxoolean-1,9-dien-28-oic Acid, with Potent Differentiating, Antiproliferative, and Anti-Inflammatory Activity1

Nanjoo Suh, Yongping Wang, Tadashi Honda, Gordon W. Gribble, Ethan Dmitrovsky, William F. Hickey, Robert A. Maue, Andrew E. Place, Donna M. Porter, Michael J. Spinella, Charlotte R. Williams, Gengfei Wu, Andrew J. Dannenberg, Kathleen C. Flanders, John J. Letterio, David J. Mangelsdorf, Carl F. Nathan, Lananh Nguyen, Weston W. Porter, Renee F. Ren, Anita B. Roberts, Nanette S. Roche, Kotha Subbaramaiah and Michael B. Sporn2

Norris Cotton Cancer Center [N. S., Y. W., E. D., A. E. P., M. J. S., C. R. W., G. W., M. B. S.] and Departments of Pharmacology [N. S., Y. W., E. D., A. E. P., M. J. S., C. R. W., G. W., M. B. S.], Pathology [W. F. H.], Physiology [R. A. M., D. M. P.], and Biochemistry [R. A. M., D. M. P.], Dartmouth Medical School, and Department of Chemistry, Dartmouth College [T. H., G. W. G.], Hanover, New Hampshire 03755; National Cancer Institute, Bethesda, Maryland 20892 [K. C. F., J. J. L., L. N., R. F. R., A. B. R., N. S. R.]; Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75235 [D. J. M., W. W. P.]; and Department of Medicine, Weill Medical College, Cornell University [A. J. D., C. F. N., K. S.], and Strang Cancer Prevention Center [A. J. D., K. S.], New York, New York 10021

The new synthetic oleanane triterpenoid 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO) is a potent, multifunctional molecule. It induces monocytic differentiation of human myeloid leukemia cells and adipogenic differentiation of mouse 3T3-L1 fibroblasts and enhances the neuronal differentiation of rat PC12 pheochromocytoma cells caused by nerve growth factor. CDDO inhibits proliferation of many human tumor cell lines, including those derived from estrogen receptor-positive and -negative breast carcinomas, myeloid leukemias, and several carcinomas bearing a Smad4 mutation. Furthermore, it suppresses the abilities of various inflammatory cytokines, such as IFN-{gamma}, interleukin-1, and tumor necrosis factor-{alpha}, to induce de novo formation of the enzymes inducible nitric oxide synthase (iNos) and inducible cyclooxygenase (COX-2) in mouse peritoneal macrophages, rat brain microglia, and human colon fibroblasts. CDDO will also protect rat brain hippocampal neurons from cell death induced by ß-amyloid. The above activities have been found at concentrations ranging from 10-6 to 10-9 M in cell culture, and these results suggest that CDDO needs further study in vivo, for either chemoprevention or chemotherapy of malignancy as well as for neuroprotection.




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Carcinogenesis, June 1, 2000; 21(6): 1183 - 1189.
[Abstract] [Full Text] [PDF]

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 Cell Growth Differ.Home page
Y. Ito, P. Pandey, A. Place, M. B. Sporn, G. W. Gribble, T. Honda, S. Kharbanda, and D. Kufe
The Novel Triterpenoid 2-Cyano-3,12-dioxoolean-1,9-dien-28-oic Acid Induces Apoptosis of Human Myeloid Leukemia Cells by a Caspase-8-dependent Mechanism
Cell Growth Differ., May 1, 2000; 11(5): 261 - 267.
[Abstract] [Full Text]

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 Cancer Res.Home page
K. Subbaramaiah, P. Michaluart, M. B. Sporn, and A. J. Dannenberg
Ursolic Acid Inhibits Cyclooxygenase-2 Transcription in Human Mammary Epithelial Cells
Cancer Res., May 1, 2000; 60(9): 2399 - 2404.
[Abstract] [Full Text]

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 CarcinogenesisHome page
M. B. Sporn and N. Suh
Chemoprevention of cancer
Carcinogenesis, March 1, 2000; 21(3): 525 - 530.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
N. Suh, Y. Wang, C. R. Williams, R. Risingsong, T. Gilmer, T. M. Willson, and M. B. Sporn
A New Ligand for the Peroxisome Proliferator-Activated Receptor-{{gamma}} (PPAR-{{gamma}}), GW7845, Inhibits Rat Mammary Carcinogenesis
Cancer Res., November 1, 1999; 59(22): 5671 - 5673.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
L. P. Henderson, L. Lin, A. Prasad, C. A. Paul, T. Y. Chang, and R. A. Maue
Embryonic Striatal Neurons from Niemann-Pick Type C Mice Exhibit Defects in Cholesterol Metabolism and Neurotrophin Responsiveness
J. Biol. Chem., June 23, 2000; 275(26): 20179 - 20187.
[Abstract] [Full Text] [PDF]


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