Curcumin inhibits COPD-like airway inflammation and lung cancer progression in mice.
Recent studies have demonstrated that K-ras mutations in lung epithelial cells elicit inflammation that promotes carcinogenesis in mice (intrinsic inflammation). The finding that patients with chronic obstructive pulmonary disease (COPD), an inflammatory disease of the lung, have an increased risk of lung cancer after controlling for smoking suggests a further link between lung cancer and extrinsic inflammation. Besides exposure to cigarette smoke, it is thought that airway inflammation in COPD is caused by bacterial colonization, particularly with non-typeable Hemophilus influenzae (NTHi). Previously, we have shown that NTHi-induced COPD-like airway inflammation promotes lung cancer in an airway conditional K-ras-induced mouse model. To further test the role of inflammation in cancer promotion, we administered the natural anti-inflammatory agent, curcumin, 1% in diet before and during weekly NTHi exposure. This significantly reduced the number of visible lung tumors in the absence of NTHi exposure by 85% and in the presence of NTHi exposures by 53%. Mechanistically, curcumin markedly suppressed NTHi-induced increased levels of the neutrophil chemoattractant keratinocyte-derived chemokine by 80% and neutrophils by 87% in bronchoalveolar lavage fluid. In vitro studies of murine K-ras-induced lung adenocarcinoma cell lines (LKR-10 and LKR-13) indicated direct anti-tumoral effects of curcumin by reducing cell viability, colony formation and inducing apoptosis. We conclude that curcumin suppresses the progression of K-ras-induced lung cancer in mice by inhibiting intrinsic and extrinsic inflammation and by direct anti-tumoral effects. These findings suggest that curcumin could be used to protract the premalignant phase and inhibit lung cancer progression in high-risk COPD patients.
Moghaddam
S J
SJ
Department of Pulmonary Medicine, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1100, Houston, TX 77030, USA. smoghadd@mdanderson.org
Barta
P
P
Mirabolfathinejad
S G
SG
Ammar-Aouchiche
Z
Z
Garza
N Torres
NT
Vo
T T
TT
Newman
Robert A
RA
Aggarwal
Bharat B
BB
Evans
Christopher M
CM
Tuvim
Michael J
MJ
Lotan
Reuben
R
Dickey
Burton F
BF
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018925:Chemokines / Q000378:metabolism; D003474:Curcumin / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D011905:Genes, ras; D006192:Haemophilus Infections / Q000150:complications; D006193:Haemophilus influenzae; D007249:Inflammation; D008175:Lung Neoplasms / Q000209:etiology* / Q000235:genetics / Q000517:prevention & control*; D008297:Male; D051379:Mice; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D018925:Chemokines; D003474:Curcumin