title: Caffeine stimulates the proliferation of human lung adenocarcinoma cells and small airway epithelial cells via activation of PKA, CREB and ERK1/2.
abstract: The incidence of pulmonary adenocarcinoma (PAC) has increased dramatically over the last three decades. Recent studies have shown that human PAC cells with phenotypic features of bronchiolar Clara cells and experimentally induced PAC of Clara cell origin are under beta-adrenergic growth control. The phosphodiesterase inhibitor, theophylline, which is contained in tea, asthma/allergy medications and numerous dietary supplements selectively stimulated the growth of this cancer type in vivo and in vitro. The current study has tested the hypothesis that another environmentally prominent phosphodiesterase inhibitor, caffeine, has similar effects. Using a cell line derived from a human PAC with Clara cell features (PACC) and immortalized human small airway epithelial cells (SAECs), our data show that caffeine activated protein kinase A (PKA), the mitogen-activated kinases ERK1/2, the nuclear transcription factor cyclic AMP response element binding protein (CREB) and stimulated cell proliferation in these cell lines. These findings suggest that exposure to caffeine may contribute to the prevalence of PAC observed today.
authors.affiliation: Experimental Oncology Laboratory, Department of Pathobiology, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA.
authors.forename: Hussein A N
authors.initials: HA
authors.lastname: Al-Wadei
authors.forename: Takashi
authors.initials: T
authors.lastname: Takahashi
authors.forename: Hildegard M
authors.initials: HM
authors.lastname: Schuller
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology*; D015153:Blotting, Western; D050882:CREB-Binding Protein / Q000187:drug effects / Q000378:metabolism; D002110:Caffeine / Q000494:pharmacology*; D045744:Cell Line, Tumor; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D017868:Cyclic AMP-Dependent Protein Kinases; D004789:Enzyme Activation / Q000187:drug effects*; D004847:Epithelial Cells / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology*; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects / Q000378:metabolism
chemical_list: D000697:Central Nervous System Stimulants; D002110:Caffeine; D050882:CREB-Binding Protein; D017346:Protein Serine-Threonine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D048049:Extracellular Signal-Regulated MAP Kinases