Caffeine stimulates the proliferation of human lung adenocarcinoma cells and small airway epithelial cells via activation of PKA, CREB and ERK1/2

Oncol Rep. 2006 Feb;15(2):431-5.


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.

MeSH terms

  • Adenocarcinoma / enzymology*
  • Blotting, Western
  • CREB-Binding Protein / drug effects
  • CREB-Binding Protein / metabolism
  • Caffeine / pharmacology*
  • Cell Line, Tumor
  • Central Nervous System Stimulants / pharmacology*
  • Cyclic AMP-Dependent Protein Kinases
  • Enzyme Activation / drug effects*
  • Epithelial Cells / drug effects*
  • Extracellular Signal-Regulated MAP Kinases / drug effects
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Humans
  • Lung Neoplasms / enzymology*
  • Protein-Serine-Threonine Kinases / drug effects
  • Protein-Serine-Threonine Kinases / metabolism


  • Central Nervous System Stimulants
  • Caffeine
  • CREB-Binding Protein
  • Protein-Serine-Threonine Kinases
  • Cyclic AMP-Dependent Protein Kinases
  • Extracellular Signal-Regulated MAP Kinases