Trans, trans-2,4-decadienal induced cell proliferation via p27 pathway in human bronchial epithelial cells

Toxicol Appl Pharmacol. 2008 Apr 1;228(1):76-83. doi: 10.1016/j.taap.2007.11.028. Epub 2007 Dec 8.


Lung cancer is the leading cause of cancer deaths worldwide. Epidemiological studies have shown that exposure to cooking oil fumes (COF) is a risk factor for lung cancer. Trans, trans-2,4-decadienal (tt-DDE), a dienaldehyde, is abundant in heated oils and COF. Previously, we found that long-term exposure (45 days) to a sub-lethal dose (1 microM) of tt-DDE significantly increased growth of human bronchial epithelial cells (BEAS-2B). Aims of this study are to understand the mechanism of tt-DDE-induced cell proliferation and possible protective effects of antioxidant, vitamin C and N-acetylcysteine (NAC) in BEAS-2B cells. Utilizing the real-time RT-PCR and Western immunoblotting, we found that p27 mRNA and protein levels were significantly increased by 1 microM tt-DDE treatment. Co-treatment with vitamin C or NAC partially prevented tt-DDE-induced cell proliferation. In addition, the downstream targets of p27, including CDK4, cyclin D1 and phosphorylated-Rb proteins, increased in 1 microM tt-DDE-treated cells and these changes were prevented by NAC co-treatment. Therefore, these results suggest that tt-DDE increased cell proliferation via inhibition of p27 expression, increase in CDK4/cyclin D1 protein accumulation and enhancement of Rb phosphorylation. Increased cell proliferation is considered as the early stages of lung carcinogenesis. Administration of antioxidants may prevent COF-associated lung carcinogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / pharmacology
  • Aldehydes / antagonists & inhibitors
  • Aldehydes / toxicity*
  • Antioxidants / pharmacology
  • Ascorbic Acid / pharmacology
  • Blotting, Western
  • Bronchi / cytology*
  • Bronchi / drug effects
  • Cell Cycle / drug effects
  • Cell Line
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects
  • Cyclin-Dependent Kinase 4 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p27 / antagonists & inhibitors
  • Cyclin-Dependent Kinase Inhibitor p27 / physiology*
  • DNA, Complementary / biosynthesis
  • DNA, Complementary / genetics
  • Epithelial Cells / drug effects*
  • Gene Expression Regulation / drug effects
  • Humans
  • Phosphorylation / drug effects
  • Reactive Oxygen Species / metabolism
  • Retinoblastoma Protein / biosynthesis
  • Retinoblastoma Protein / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / drug effects*


  • Aldehydes
  • Antioxidants
  • DNA, Complementary
  • Reactive Oxygen Species
  • Retinoblastoma Protein
  • Cyclin-Dependent Kinase Inhibitor p27
  • 2,4-decadienal
  • Cyclin-Dependent Kinase 4
  • Ascorbic Acid
  • Acetylcysteine