Research Article| Volume 45, ISSUE 7, P1257-1264, May 2009

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

  • Hussein A.N. Al-Wadei
    Experimental Oncology Laboratory, Department of Pathobiology, College of Veterinary Medicine, University of Tennessee, 2407 River Drive, Knoxville, TN 37996, USA

    Sana’a University, Sana’a, Yemen
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  • Hildegard M. Schuller
    Corresponding author: Tel.: +1 865 974 8217; fax: +1 865 974 5616.
    Experimental Oncology Laboratory, Department of Pathobiology, College of Veterinary Medicine, University of Tennessee, 2407 River Drive, Knoxville, TN 37996, USA
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Published:March 02, 2009DOI:



      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.


      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.


      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.


      Our data suggest that β-carotene promotes the development of PAC via increased cAMP signalling.


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