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Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate DMBA-TPA
Published on: December 19, 2019
beta-Carotene promotes the development of NNK-induced small airway-derived lung adenocarcinoma
Hussein A N Al-Wadei1, Hildegard M Schuller2
1Experimental 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.
Aim:
beta-Carotene has shown cancer-preventive effects in preclinical studies while increasing lung cancer mortality in clinical trials. We have shown that beta-carotene stimulates cAMP signalling in vitro. Here, we have tested the hypothesis that beta-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 beta-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:
beta-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 beta-carotene promotes the development of PAC via increased cAMP signalling.
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