beta-Carotene promotes the development of NNK-induced small airway-derived lung adenocarcinoma.
OBJECTIVE
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.
Al-Wadei
Hussein A N
HAN
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.
Schuller
Hildegard M
HM
Experimental Oncology Laboratory, Department of Pathobiology, College of Veterinary Medicine, University of Tennessee, 2407 River Drive, Knoxville, TN 37996, USA. Electronic address: hmsch@utk.edu.
D000230:Adenocarcinoma / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001681:Biological Assay / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D006224:Cricetinae; D000242:Cyclic AMP / Q000032:analysis / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000032:analysis / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000032:analysis / Q000378:metabolism; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008647:Mesocricetus; D023421:Models, Animal; D009602:Nitrosamines; D010766:Phosphorylation; D011897:Random Allocation; D012176:Retinoids / Q000097:blood; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D019207:beta Carotene / Q000009:adverse effects* / Q000494:pharmacology
D017362:Cyclic AMP Response Element-Binding Protein; D009602:Nitrosamines; D012176:Retinoids; D019207:beta Carotene; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; D000242:Cyclic AMP; D048049:Extracellular Signal-Regulated MAP Kinases