A novel synthetic oleanane triterpenoid, 2-cyano-3,12-dioxoolean-1,9- dien-28-oic acid, with potent differentiating, antiproliferative, and anti- inflammatory activity

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. RenAnita B. Roberts, Nanette S. Roche, Kotha Subbaramaiah, Michael B. Sporn

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Abstract

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-I,1 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-γ interleukin-1, and tumor necrosis factor-α, 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 β-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.

Original languageEnglish (US)
Pages (from-to)336-341
Number of pages6
JournalCancer Research
Volume59
Issue number2
Publication statusPublished - Jan 16 1999

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Suh, N., Wang, Y., Honda, T., Gribble, G. W., Dmitrovsky, E., Hickey, W. F., ... Sporn, M. B. (1999). A novel synthetic oleanane triterpenoid, 2-cyano-3,12-dioxoolean-1,9- dien-28-oic acid, with potent differentiating, antiproliferative, and anti- inflammatory activity. Cancer Research, 59(2), 336-341.