Lung tumor promotion by curcumin.
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.
Department of Cancer Biology, Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Stephanie T
ST
Dance-Barnes
Nancy D
ND
Kock
Joseph E
JE
Moore
Elaine Y
EY
Lin
Libyadda J
LJ
Mosley
Ralph B
RB
D'Agostino
Thomas P
TP
McCoy
Alan J
AJ
Townsend
Mark Steven
MS
Miller
D000818:Animals; D016588:Anticarcinogenic Agents / Q000009:adverse effects / Q000494:pharmacology*; D002084:Butylated Hydroxytoluene / Q000633:toxicity; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D003474:Curcumin / Q000009:adverse effects / Q000494:pharmacology*; D004318:Doxycycline / Q000494:pharmacology; D011905:Genes, ras; D008175:Lung Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009928:Organ Specificity; D017382:Reactive Oxygen Species / Q000378:metabolism; D013467:Sulindac / Q000494:pharmacology
D016588:Anticarcinogenic Agents; D017382:Reactive Oxygen Species; D013467:Sulindac; D002084:Butylated Hydroxytoluene; D003474:Curcumin; D004318:Doxycycline