Eudesmol isomers induce caspase-mediated apoptosis in human hepatocellular carcinoma HepG2 cells

Basic Clin Pharmacol Toxicol. 2013 Nov;113(5):300-6. doi: 10.1111/bcpt.12097. Epub 2013 Jul 2.


Eudesmols are naturally occurring sesquiterpenoid alcohols that present cytotoxic effect to cancer cells. Herein, all eudesmol isomers displayed cytotoxicity to different tumour cell lines. α-Eudesmol showed IC₅₀ values ranging from 5.38 ± 1.10 to 10.60 ± 1.33 μg/mL for B16-F10 and K562 cell lines, β-eudesmol showed IC₅₀ values ranging from 16.51 ± 1.21 to 24.57 ± 2.75 μg/mL for B16-F10 and HepG2 cell lines, and γ-eudesmol showed IC₅₀ values ranging from 8.86 ± 1.27 to 15.15 ± 1.06 μg/mL for B16-F10 and K562 cell lines, respectively. In addition, in this work, we studied the mechanisms of cytotoxic action of eudesmol isomers (α-, β- and γ-eudesmol) in human hepatocellular carcinoma HepG2 cells. After 24-hr incubation, HepG2 cells treated with eudesmol isomers presented typical hallmarks of apoptosis, as observed by morphological analysis in cells stained with haematoxylin-eosin and acridine orange/ethidium bromide. None of eudesmol isomers caused membrane disruption at any concentration tested. Moreover, eudesmol isomers induced loss of mitochondrial membrane potential and an increase in caspase-3 activation in HepG2 cells, suggesting the induction of caspase-mediated apoptotic cell death. In conclusion, the eudesmol isomers herein investigated are able to reduce cell proliferation and to induce tumour cell death by caspase-mediated apoptosis pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Cell Membrane / drug effects
  • Cell Proliferation / drug effects
  • Hep G2 Cells
  • Humans
  • Inhibitory Concentration 50
  • K562 Cells
  • Membrane Potential, Mitochondrial / drug effects
  • Sesquiterpenes, Eudesmane / pharmacology*


  • Sesquiterpenes, Eudesmane
  • gamma-eudesmol
  • beta-eudesmol
  • alpha-eudesmol
  • CASP3 protein, human
  • Caspase 3