The Rexinoids LG100268 and LG101506 Inhibit Inflammation and Suppress Lung Carcinogenesis in A/J Mice.

[en] LG101506 was originally synthesized to overcome some of the undesirable side effects of rexinoids. We compared the anticarcinogenic action of LG101506 and LG100268 and for the first time showed that both drugs are useful for prevention of lung cancer in A/J mice. These molecules markedly reduced tumor number, tumor size, and total tumor burden, when chronically administered to A/J mice that had been initiated with the mutagenic carcinogen, vinyl carbamate. Moreover, LG100268 synergized with the histone deacetylase inhibitor, vorinostat, for prevention of experimental lung cancer and enhanced the effect of carboplatin/paclitaxel for treatment of experimental lung cancer. Both rexinoids diminished the percentage of high-grade, highly malignant adenocarcinomas found at autopsy. In cell culture studies, the rexinoids exhibited potent anti-inflammatory properties at nanoMolar concentrations. These drugs suppressed the ability of lipopolysaccharide to stimulate the synthesis and secretion of nitric oxide and inflammatory cytokines and chemokines, such as IL6, IL1beta, CXCL2, and CSF3, in macrophage-like RAW264.7 cells. The present results suggest that LG100268, LG101506, or a related rexinoid may have useful clinical applications in the field of oncology. Cancer Prev Res; 9(1); 105-14. (c)2015 AACR.

Disciplines :

Pharmacy, pharmacology & toxicology

Author, co-author :

Cao, Martine ; Dartmouth Medical School

Royce, Darlene B.

Risingsong, Renee

Williams, Charlotte R.

Sporn, Michael B.

Liby, Karen T.

Language :

English

Title :

The Rexinoids LG100268 and LG101506 Inhibit Inflammation and Suppress Lung Carcinogenesis in A/J Mice.

Publication date :

2016

Journal title :

Cancer Prevention Research

ISSN :

1940-6207

eISSN :

1940-6215

Publisher :

American Association for Cancer Research, Philadelphia, United States - Pennsylvania

Volume :

Issue :

Pages :

105-14

Peer reviewed :

Peer Reviewed verified by ORBi

Commentary :

Available on ORBi :

since 25 January 2016

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