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Curcumin inhibits COPD-like airway inflammation and lung cancer progression in mice.
- Source :
-
Carcinogenesis [Carcinogenesis] 2009 Nov; Vol. 30 (11), pp. 1949-56. Date of Electronic Publication: 2009 Sep 30. - Publication Year :
- 2009
-
Abstract
- 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.
- Subjects :
- Animals
Anti-Inflammatory Agents, Non-Steroidal therapeutic use
Antineoplastic Agents therapeutic use
Apoptosis drug effects
Cell Line, Tumor
Cell Proliferation drug effects
Cell Survival drug effects
Chemokines metabolism
Curcumin therapeutic use
Female
Genes, ras
Haemophilus Infections complications
Inflammation
Lung Neoplasms genetics
Male
Mice
Neutrophils metabolism
Neutrophils pathology
Pulmonary Disease, Chronic Obstructive drug therapy
Pulmonary Disease, Chronic Obstructive physiopathology
Anti-Inflammatory Agents, Non-Steroidal pharmacology
Antineoplastic Agents pharmacology
Curcumin pharmacology
Haemophilus influenzae
Lung Neoplasms etiology
Lung Neoplasms prevention & control
Pulmonary Disease, Chronic Obstructive complications
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2180
- Volume :
- 30
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Carcinogenesis
- Publication Type :
- Academic Journal
- Accession number :
- 19793800
- Full Text :
- https://doi.org/10.1093/carcin/bgp229