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Cancer Prev Res (Phila). 2009 Dec;2(12):1050-8. doi: 10.1158/1940-6207.CAPR-09-0085. Epub 2009 Dec 1.

Triterpenoids CDDO-methyl ester or CDDO-ethyl amide and rexinoids LG100268 or NRX194204 for prevention and treatment of lung cancer in mice.

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1
Department of Pharmacology, Dartmouth Medical School, Hanover, NH 03755, USA. karen.liby@dartmouth.edu

Abstract

We tested members of two noncytotoxic classes of drugs, synthetic oleanane triterpenoids and rexinoids, both as individual agents and in combination, for the prevention and treatment of carcinogenesis in a highly relevant animal model of lung cancer. Lung adenocarcinomas were induced in A/J mice by injection of the carcinogen vinyl carbamate. Mice were fed drugs in diet, beginning 1 week after the carcinogen challenge for prevention or 8 weeks later for treatment. The number, size, and severity of tumors in the lungs were then evaluated. In the prevention studies, the triterpenoids CDDO-ethyl amide and CDDO-methyl ester reduced the average tumor burden (ATB) in the lungs 86% to 92%, respectively, compared with the controls, and the rexinoid LG100268 (268) reduced ATB by 50%. The combination of CDDO-ethyl amide and 268 reduced ATB by 93%. We show for the first time that these drugs also were highly effective for treatment of experimental lung cancer, and all triterpenoid and rexinoid combinations reduced ATB 85% to 87% compared with the control group. The triterpenoids also potently inhibited proliferation of VC1 mouse lung carcinoma cells and directly interacted with key regulatory proteins in these cells. In contrast, the rexinoids had little antiproliferative activity in VC1 cells but were potent inhibitors of the toll-like receptor pathway in macrophage-like cells. Triterpenoids and rexinoids are multifunctional, well-tolerated drugs that target different signaling pathways and are thus highly effective for prevention and treatment of experimental lung cancer.

PMID:
19952361
PMCID:
PMC2818234
DOI:
10.1158/1940-6207.CAPR-09-0085
[Indexed for MEDLINE]
Free PMC Article

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