Toxic effects of some conifer resin acids and tea tree oil on human epithelial and fibroblast cells

Toxicology. 1996 Feb 22;107(2):99-109. doi: 10.1016/0300-483x(95)03242-8.


The present study was undertaken to assess and compare the in vitro cytotoxic effects of three resin acid analogues: dehydrobietic acid, podocarpic acid, O-methylpodocarpic acid; an essential oil from Australia (tea tree oil); and tapped oleoresin from Thailand, on human epithelial and fibroblast cells, using a quantitative neutral red spectrophotometric assay. All of the investigated compounds except for tea tree oil exhibited a cytotoxic activity which was proportional to their concentrations and time of exposure up to 24 h, i.e. higher concentrations and longer time of exposure caused increased cell death. Dehydroabietic acid and the oleoresin were the most toxic compounds followed by O-methylpodocarpic acid, whereas podocarpic acid and tea tree oil showed a lower level of toxicity. On the basis on these findings it is concluded that an isopropyl group on the aromatic C-ring is of great importance for the cytotoxicity of the tested abietane resin acids, thus indicating that the cytotoxic activity of oleoresins most probably is caused by synergistic or additive effects of resin acids. The results from this work support the view that antibacterial activity parallels cytotoxic activity which suggests a similar mode of action, most probably exerted by membrane-associated reactions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abietanes*
  • Anti-Infective Agents, Local / toxicity*
  • Cell Death / drug effects
  • Cell Division / drug effects
  • Cells, Cultured
  • Diterpenes / toxicity
  • Dose-Response Relationship, Drug
  • Epithelial Cells*
  • Epithelium / drug effects
  • Fibroblasts / cytology*
  • Fibroblasts / drug effects
  • Humans
  • Microbial Sensitivity Tests
  • Neutral Red
  • Oils, Volatile / toxicity*
  • Phenanthrenes / toxicity
  • Plant Oils / chemistry
  • Plant Oils / toxicity*
  • Resins, Plant / pharmacology
  • Resins, Plant / toxicity*
  • Staphylococcus aureus / drug effects
  • Structure-Activity Relationship
  • Tea Tree Oil
  • Terpenes / chemistry
  • Terpenes / toxicity
  • Trees / chemistry


  • Abietanes
  • Anti-Infective Agents, Local
  • Diterpenes
  • Oils, Volatile
  • Phenanthrenes
  • Plant Oils
  • Resins, Plant
  • Terpenes
  • dehydroabietic acid
  • Neutral Red
  • Tea Tree Oil
  • podocarpic acid