Kahweol blocks STAT3 phosphorylation and induces apoptosis in human lung adenocarcinoma A549 cells

Toxicol Lett. 2009 May 22;187(1):28-34. doi: 10.1016/j.toxlet.2009.01.022. Epub 2009 Jan 24.


Kahweol, the coffee-specific diterpene, has been reported to have anti-carcinogenic properties. Animal data support such a chemopreventive effect of coffee. However, the precise underlying protective mechanisms are poorly understood. In this study, the apoptotic effect of kahweol in human lung adenocarcinoma A549 cells was investigated. In cell viability assays and cell proliferation assays, kahweol exhibited anti-proliferative and pro-apoptotic effects on A549 cells in a time- and dose-dependent manner. Kahweol considerably inhibited the expression of Bcl-2 but increased that of Bax; it also stimulated the cleavage of caspase-3 and PARP (poly ADP-ribose polymerase). In addition, kahweol-induced apoptosis was confirmed by TUNEL assays. Furthermore, kahweol inhibited dose-dependent phosphorylation of signal transducer and activator of transcription 3 (STAT3). An overexpression in STAT3 led to resistance to kahweol-induced apoptosis, suggesting that STAT3 was a critical target of kahweol. These findings suggest that kahweol inhibited A549 cell growth and induced apoptosis via down-regulation of STAT3 signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology*
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Diterpenes / pharmacology*
  • Dose-Response Relationship, Drug
  • Down-Regulation / drug effects
  • Drug Screening Assays, Antitumor
  • Humans
  • In Situ Nick-End Labeling
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Mitochondria / drug effects
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction / drug effects
  • Time Factors
  • Tumor Cells, Cultured
  • bcl-2-Associated X Protein / metabolism


  • Antineoplastic Agents
  • BAX protein, human
  • Diterpenes
  • Proto-Oncogene Proteins c-bcl-2
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • bcl-2-Associated X Protein
  • kahweol