Cytotoxic activity of guaiazulene on gingival fibroblasts and the influence of light exposure on guaiazulene-induced cell death

Toxicol In Vitro. 2011 Feb;25(1):64-72. doi: 10.1016/j.tiv.2010.09.008. Epub 2010 Sep 18.


Guaiazulene (GA) is widely used as a natural ingredient in many health care products and solutions. Although it has been reported to have interesting biological effects, GA and azulene derivatives have been proven to be cytotoxic against normal human cells and human tumor cells; moreover, guaiazulene has shown photomutagenic properties on bacterial strains. Therefore, we evaluated and compared the cytotoxicity of GA at different concentrations on human gingival fibroblast (HGF) cell cultures under normal conditions and under UV irradiation (UV-A dose: 6.4 J/cm(2)). The compound tested was found to significantly reduce cell viability (dose-dependent trend, IC(50) 72.1 μM), decrease protein procollagen α1 type I synthesis, a marker for HGF protein, and COL1A1 mRNA expression. The cytotoxic effects were accompanied by activation of an intrinsic apoptotic pathway, studied using transmission electron microscopy (TEM) and caspase-3 activation. The light exposure of the cell culture treated decreased GA-induced cell death (IC(50) 128.9 μM), suggesting a photoprotective effect due to the photodegradation of the toxic agent, guaiazulene. Furthermore, the products of the photodegradation reaction of GA proved not to be toxic against HGFs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Azulenes / radiation effects*
  • Azulenes / toxicity*
  • Biomarkers / metabolism
  • Caspase 3 / metabolism
  • Cell Survival / drug effects
  • Cells, Cultured
  • Collagen Type I / genetics
  • Collagen Type I / metabolism
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Fibroblasts / ultrastructure
  • Gene Expression Regulation / drug effects
  • Gingiva / cytology
  • Gingiva / drug effects*
  • Gingiva / metabolism
  • Gingiva / ultrastructure
  • Humans
  • Inhibitory Concentration 50
  • Oxidants, Photochemical / radiation effects*
  • Oxidants, Photochemical / toxicity*
  • Photolysis
  • RNA, Messenger / metabolism
  • Sesquiterpenes / radiation effects*
  • Sesquiterpenes / toxicity*
  • Sesquiterpenes, Guaiane
  • Ultraviolet Rays*


  • Azulenes
  • Biomarkers
  • Collagen Type I
  • Oxidants, Photochemical
  • RNA, Messenger
  • Sesquiterpenes
  • Sesquiterpenes, Guaiane
  • collagen type I, alpha 1 chain
  • guaiazulene
  • CASP3 protein, human
  • Caspase 3