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Cancer Biol Ther. 2008 May;7(5):709-17. Epub 2008 May 7.

Human neuroblastoma cells rapidly enter cell cycle arrest and apoptosis following exposure to C-28 derivatives of the synthetic triterpenoid CDDO.

Author information

1
Department of Pediatrics, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio 44106, USA.

Abstract

Synthetic triterpenoids, such as 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO) and its derivatives, are an extremely potent class of new anti-cancer therapeutic agents, characterized by high anti-tumor potency and low toxicity to normal tissues. This report is the first to investigate the effects of C-28 derivatives of CDDO on 22 pediatric solid tumor cell lines, including neuroblastoma, rhabdomyosarcoma, osteosarcoma, and Ewing's sarcoma. We determined IC(50)s in the range of 5-170 nM for inhibition of colony formation and DNA synthesis, and 110-630 nM for metabolic cell death and decrease in cell number, using the C-28 CDDO analogs, CDDO methyl ester (CDDO-Me), CDDO imidazolide (CDDO-Im), CDDO ethyl amide (CDDO-EA), CDDO trifluoroethyl amide (CDDO-TFEA), and CDDO diethylamide (CDDO-DE). After treatment of human neuroblastoma cells with CDDO-Me, cell cycle studies show depletion of the S-phase, while apoptosis studies show conformational activation and mitochondrial translocation of Bax protein, as well as activation of caspases -3 and -8. These data demonstrate the potential utility of CDDO analogs as promising novel therapeutic agents for high-risk pediatric solid tumors.

PMID:
18277094
PMCID:
PMC2727860
DOI:
10.4161/cbt.7.5.5713
[Indexed for MEDLINE]
Free PMC Article

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