title: Modulation by licofelone and celecoxib of experimentally induced cancer and preneoplastic lesions in mice exposed to cigarette smoke.
abstract: Chronic inflammation plays a crucial role in cigarette smoke-related carcinogenesis. Accordingly, anti-inflammatory agents, such as nonsteroidal anti-inflammatory drugs (NSAIDs), provide a rational strategy in cancer chemoprevention. We assayed celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, and licofelone, an inhibitor of COX-1, COX-2, and 5- lipoxygenase (5-LOX), for the ability to modulate carcinogenesis in neonatal mice exposed to mainstream cigarette smoke (MCS) for 4 months and thereafter kept in filtered air for 3.5 months. A preliminary toxicity study and a chemoprevention study involved the use of 591 Swiss H mice. Exposure to MCS caused a variety of pulmonary emphysema, alveolar and bronchial epithelial hyperplasias, proliferation of blood vessels, microadenomas, adenomas and malignant tumors, as well as kidney tubular and urinary bladder papillary epithelial hyperplasias. Celecoxib (1600 mg/kg diet) and even better licofelone (960 mg/kg diet) were able to significantly attenuate the MCS-induced alterations of inflammatory nature, including pulmonary emphysema, alveolar epithelial hyperplasias and microadenomas and urinary tract hyperplastic lesions when given to mice according to a protocol that mimics an intervention in current smokers. Moreover, celecoxib attenuated the yield of lung adenomas and both NSAIDs showed some involvement in lowering the progression to cancer in the lung. Celecoxib exhibited some protective effects even when given according to a protocol involving its administration after discontinuation of exposure to MCS. However, both agents and especially celecoxib showed some hepatotoxicity and affected survival and body weight gain of mice when administered to MCS-exposed mice in the long term.
authors: Roumen
authors: R
authors: Balansky
authors: Gancho
authors: G
authors: Ganchev
authors: Marietta
authors: M
authors: Iltcheva
authors: Manasi
authors: M
authors: Nikolov
authors: Sebastiano
authors: S
authors: La Maestra
authors: Rosanna T
authors: RT
authors: Micale
authors: Francesco
authors: F
authors: D'Agostini
authors: Vernon E
authors: VE
authors: Steele
authors: Department of Health Sciences, University of Genoa, via A. Pastore 1, 16132 Genoa, Italy. sdf@unige.it.
authors: Silvio
authors: S
authors: De Flora
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D000068579:Celecoxib / Q000494:pharmacology*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D008175:Lung Neoplasms / Q000139:chemically induced / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D008297:Male; D051379:Mice; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D011230:Precancerous Conditions / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D011758:Pyrroles / Q000494:pharmacology*; D012907:Smoking / Q000009:adverse effects*; D015996:Survival Rate; D059550:Toxicity Tests, Subchronic / Q000379:methods
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016588:Anticarcinogenic Agents; D052246:Cyclooxygenase 2 Inhibitors; D004791:Enzyme Inhibitors; D011758:Pyrroles; D000068579:Celecoxib; C088092:licofelone