β-Carotene promotes the development of NNK-induced small airway-derived lung adenocarcinoma

• Published in: European journal of cancer (1990) Vol. 45; no. 7; pp. 1257 - 1264
• Main Authors: Al-Wadei, Hussein A.N, Schuller, Hildegard M
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01.05.2009; Elsevier
• Subjects: Adenocarcinoma - chemically induced; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Animals; beta Carotene - adverse effects; beta Carotene - pharmacology; Biological and medical sciences; Biological Assay - methods; Blotting, Western - methods; cAMP signalling; Cricetinae; Cyclic AMP - analysis; Cyclic AMP - metabolism; Cyclic AMP Response Element-Binding Protein - analysis; Cyclic AMP Response Element-Binding Protein - metabolism; Extracellular Signal-Regulated MAP Kinases - analysis; Extracellular Signal-Regulated MAP Kinases - metabolism; Hematology, Oncology and Palliative Medicine; Lung adenocarcinoma; Lung Neoplasms - chemically induced; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Male; Medical sciences; Mesocricetus; Models, Animal; Nitrosamines; Pharmacology. Drug treatments; Phosphorylation; Random Allocation; Retinoids - blood; Signal Transduction - drug effects; Time Factors; Tumors; Tumour promotion; β-Carotene; cAMP signalling; Lung adenocarcinoma; Tumour promotion; β-Carotene; Lung disease; Respiratory disease; Lung cancer; Nitrosamine; Cyclic AMP; Malignant tumor; Bronchopulmonary adenocarcinoma; Respiratory system; Respiratory tract; Carcinogen; Signal transduction; Cancerology; Bronchus disease; Betacarotene; Cancer
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2008.10.035

Abstract Aim β-Carotene has shown cancer-preventive effects in preclinical studies while increasing lung cancer mortality in clinical trials. We have shown that β-carotene stimulates cAMP signalling in vitro . Here, we have tested the hypothesis that β-carotene promotes the development of pulmonary adenocarcinoma (PAC) in vivo via cAMP signalling. Methods PAC was induced in hamsters with the carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), followed by β-carotene for 1.5 years. Incidence, multiplicity and size of lung tumours were recorded, and phosphorylated CREB and ERK1/2 in tumour cells were determined by Western blots. Cyclic AMP in blood cells was analysed by immunoassays, retinoids in serum and lungs by HPLC. Results β-Carotene increased lung tumour multiplicity, lung tumour size, blood cell cAMP, serum and lung levels of retinoids and induced p-CREB and p-ERK1/2 in lung tumours. Conclusions Our data suggest that β-carotene promotes the development of PAC via increased cAMP signalling.