Involvement of p21WAF1/CIP1, pRB, Bax and NF-kappaB in induction of growth arrest and apoptosis by resveratrol in human lung carcinoma A549 cells

Int J Oncol. 2003 Oct;23(4):1143-9.


Resveratrol, a polyphenolic phytoalexin found in grapes, may have the potential for prevention and therapy for human cancer. We report here that resveratrol inhibits the growth of human lung carcinoma A549 cells and provides molecular understanding of this effect. Resveratrol treatment of A549 cells resulted in a concentration-dependent induction of S phase arrest in cell cycle progression. This anti-proliferative effect of resveratrol was associated with a marked inhibition of the phosphorylation of the retinoblastoma protein (pRB) and concomitant induction of cyclin-dependent kinase (Cdk) inhibitor p21WAF1/CIP, which appears to be transcriptionally upregulated and is p53- dependent. In addition, resveratrol treatment resulted in induction of apoptosis as determined by fluorescence microscopy and flow cytometric analysis. These effects were found to correlate with an activation of caspase-3 and a shift in Bax/Bcl-xL ratio more towards apoptosis. Resveratrol treatment also inhibited the transcriptional activity of nuclear transcription factor kappaB (NF-kappaB). Taken together, these findings suggest that resveratrol has strong potential for development as an agent for prevention against human lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology
  • Apoptosis*
  • Blotting, Western
  • Caspase 3
  • Caspases / metabolism
  • Cell Cycle
  • Cell Death
  • Cell Division
  • Cell Line, Tumor
  • Cell Nucleus / metabolism
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / metabolism*
  • Dose-Response Relationship, Drug
  • Flow Cytometry
  • Humans
  • Models, Biological
  • NF-kappa B / metabolism*
  • Phosphorylation
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-bcl-2*
  • Resveratrol
  • Retinoblastoma Protein / metabolism*
  • S Phase
  • Stilbenes / pharmacology*
  • Time Factors
  • Transcription, Genetic
  • Transfection
  • Tumor Suppressor Protein p53 / metabolism
  • Up-Regulation
  • bcl-2-Associated X Protein


  • Antineoplastic Agents, Phytogenic
  • BAX protein, human
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • NF-kappa B
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Retinoblastoma Protein
  • Stilbenes
  • Tumor Suppressor Protein p53
  • bcl-2-Associated X Protein
  • CASP3 protein, human
  • Caspase 3
  • Caspases
  • Resveratrol