[Rich66]

1: Carcinogenesis. 2009 Apr 9. [Epub ahead of print]

Lung tumor promotion by curcumin.

Dance-Barnes ST, Kock ND, Moore JE, Lin EY, Mosley LJ, D'Agostino RB Jr, McCoy TP, Townsend AJ, Miller MS.
Department of Cancer Biology.
Curcumin exhibits anti-inflammatory and anti-tumor activity and is being tested in clinical trials as a chemopreventive agent for colon cancer. Curcumin's chemopreventive activity was tested in a transgenic mouse model of lung cancer that expresses the human Ki-ras(G12C) allele in a doxycycline (DOX) inducible and lung-specific manner. The effects of curcumin were compared to the lung tumor promoter, butylated hydroxytoluene (BHT), and the lung cancer chemopreventive agent, sulindac. Treatment of DOX-induced mice with dietary curcumin increased tumor multiplicity (36.3+/-0.9 vs. 24.3+/-0.2) and progression to later stage lesions, results which were similar to animals that were co-treated with DOX/BHT. Microscopic examination showed that the percentage of lung lesions that were adenomas and adenocarcinomas increased to 66% in DOX/BHT, 66% in DOX/curcumin, and 49% in DOX/BHT/curcumin treated groups relative to DOX only treated mice (19%). Immunohistochemical analysis also showed increased evidence of inflammation in DOX/BHT, DOX/curcumin, and DOX/BHT/curcumin mice relative to DOX only treated mice. In contrast, co-treatment of DOX/BHT mice with 80 ppm of sulindac inhibited the progression of lung lesions and reduced the inflammation. Lung tissue from DOX/curcumin treated mice demonstrated a significant increase (33%; p = 0.01) in oxidative damage, as assessed by the levels of carbonyl protein formation, relative to DOX-treated control mice after one week on the curcumin diet. These results suggest that curcumin may exhibit organ-specific effects to enhance reactive oxygen species formation in the damaged lung epithelium of smokers and ex-smokers. Ongoing clinical trials thus may need to exclude smokers and ex-smokers in chemopreventive trials of curcumin.