Lung tumor promotion by curcumin.

Abstract

Curcumin exhibits anti-inflammatory and antitumor 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 with 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 versus 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 200 p.p.m. [DOSAGE ERROR CORRECTED] 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 1 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.

• Authors: Stephanie T Dance-Barnes, Nancy D Kock, Joseph E Moore, Elaine Y Lin, Libyadda J Mosley, Ralph B D'Agostino Jr, Thomas P McCoy, Alan J Townsend, Mark Steven Miller
• Journal: Carcinogenesis (Carcinogenesis) Vol. 30 Issue 6 Pg. 1016-23 (Jun 2009) ISSN: 1460-2180 [Electronic] England
• PMID: 19359593 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Anticarcinogenic Agents
• Reactive Oxygen Species
• Sulindac
• Butylated Hydroxytoluene
• Curcumin
• Doxycycline

Topics

• Animals
• Anticarcinogenic Agents (adverse effects, pharmacology)
• Butylated Hydroxytoluene (toxicity)
• Cell Transformation, Neoplastic (drug effects)
• Curcumin (adverse effects, pharmacology)
• Doxycycline (pharmacology)
• Genes, ras
• Lung Neoplasms (chemically induced, drug therapy, metabolism, pathology)
• Mice
• Mice, Transgenic
• Organ Specificity
• Reactive Oxygen Species (metabolism)
• Sulindac (pharmacology)