The synthetic oleanane triterpenoid, CDDO-methyl ester, is a potent antiangiogenic agent

Nicola Vannini, Girieca Lorusso, Rosaria Cammarota, Massimo Barberis, Douglas M. Noonan, Michael B. Sporn, Adriana Albini

Research output: Contribution to journalArticlepeer-review

Abstract

We show that the synthetic oleanane triterpenoid, CDDO-methyl ester (CDDO-Me; methyl 2-cyano-3,12-dioxoolean-1,9-dien-28-oate) is an effective agent for suppressing angiogenesis, both in cell culture and in vivo. The potency of CDDO-Me is particularly strikingwhen dosed in vivo to inhibit the angiogenic effects of vascular endothelial growth factor and tumor necrosis factor-α in Matrigel sponge assays; activity is seen at i.p. doses of CDDO-Me as low as 0.003 mg/kg of body weight. If the Matrigel sponges are impregnated with CDDO-Me just before implantation in the mice, picomolar doses of CDDO-Me will suppress angiogenesis. CDDO-Me also inhibits growth of endothelial cells in monolayer cultures and suppresses neovascular morphogenesis in three-dimensional cultures, but significantly higher doses (50-200 nmol/L) are required. We also show antiangiogenic effects of CDDO-Me on xenografts of Kaposi's sarcoma cells in immunocompromised mice, using CD31 as a marker. Several known individual molecular targets of CDDO-Me and related triterpenoids that are relevant to all of these findings include nuclear factor-κB signaling, signal transducers and activators of transcription signaling, and transformingg rowth factor-β signaling, as well as Keap1, the endogenous inhibitor of the transcription factor Nrf2. However, the particularly potent antiangiogenic activity seen in vivo in the present experiments suggest that CDDO-Me, as an angioprevention agent, may be interacting with an entire network of molecular and cellular targets, rather than at a single molecular locus or in a single-cell type.

Original languageEnglish
Pages (from-to)3139-3146
Number of pages8
JournalMolecular Cancer Therapeutics
Volume6
Issue number12
DOIs
Publication statusPublished - Dec 1 2007

ASJC Scopus subject areas

  • Oncology
  • Drug Discovery
  • Pharmacology

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