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.
Keywords
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Article info
Publication history
Published online: March 02, 2009
Accepted:
October 28,
2008
Received in revised form:
October 22,
2008
Received:
July 30,
2008
Footnotes
☆Supported by RO1CA096128 with the National Cancer Institute.
Identification
Copyright
© 2008 Elsevier Ltd. Published by Elsevier Inc. All rights reserved.
