Modulation by Licofelone and Celecoxib of Experimentally Induced Cancer and Preneoplastic Lesions in Mice Exposed to Cigarette Smoke
Sebastiano La Maestra,
Rosanna T. Micale,
Vernon E. Steele,
Silvio De Flora.
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.
Keywords: Celecoxib, chemoprevention, cigarette smoke, licofelone, lung tumors.
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