Lung tumor promotion by curcumin

Stephanie T. Dance-Barnes, Nancy D. Kock, Joseph E. Moore, Elaine Y. Lin, Libyadda J. Mosley, Ralph B. D'Agostino, Thomas P. Mccoy, Alan J. Townsend, Mark Steven Miller

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61 Scopus citations

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-rasG12C 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 80 p.p.m. 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.

Original languageEnglish (US)
Pages (from-to)1016-1023
Number of pages8
JournalCarcinogenesis
Volume30
Issue number6
DOIs
StatePublished - 2009

ASJC Scopus subject areas

  • Cancer Research

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    Dance-Barnes, S. T., Kock, N. D., Moore, J. E., Lin, E. Y., Mosley, L. J., D'Agostino, R. B., Mccoy, T. P., Townsend, A. J., & Miller, M. S. (2009). Lung tumor promotion by curcumin. Carcinogenesis, 30(6), 1016-1023. https://doi.org/10.1093/carcin/bgp082