Eupalmerin acetate, a novel anticancer agent from Caribbean gorgonian octocorals, induces apoptosis in malignant glioma cells via the c-Jun NH2-terminal kinase pathway

Mol Cancer Ther. 2007 Jan;6(1):184-92. doi: 10.1158/1535-7163.MCT-06-0422.


The marine ecosystem is a vast but largely untapped resource for potential naturally based medicines. We tested 15 compounds derived from organisms found in the Caribbean Sea (14 gorgonian octocoral-derived compounds and one sponge-derived compound) for their anticancer effects on human malignant glioma U87-MG and U373-MG cells. Eupalmerin acetate (EPA) was chosen as the lead compound based on its longer-term stability and greater cytotoxicity than those of the other compounds we tested in these cell types. EPA induced G(2)-M cell cycle arrest and apoptosis via the mitochondrial pathway; it translocated Bax from the cytoplasm to the mitochondria and dissipated the mitochondrial transmembrane potential in both cell types. EPA was found to increase phosphorylated c-Jun NH(2)-terminal kinase (JNK) by >50% in both U87-MG and U373-MG cells. A specific JNK inhibitor, SP600125, inhibited EPA-induced apoptosis, confirming the involvement of the JNK pathway in EPA-induced apoptotic cell death. Furthermore, 7 days of daily intratumoral injections of EPA significantly suppressed the growth of s.c. malignant glioma xenografts (P < 0.01, on day 19). These results indicate that EPA is therapeutically effective against malignant glioma cells in vitro and in vivo and that it, or a similar marine-based compound, may hold promise as a clinical anticancer agent.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anthozoa / chemistry*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Caribbean Region
  • Diterpenes / chemistry
  • Diterpenes / pharmacology*
  • Enzyme Activation / drug effects
  • Female
  • G2 Phase / drug effects
  • Glioma / enzymology
  • Glioma / metabolism*
  • Glioma / pathology*
  • Humans
  • Inhibitory Concentration 50
  • Injections, Subcutaneous
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • Membrane Potentials / drug effects
  • Mice
  • Mice, Nude
  • Mitochondria / drug effects
  • Mitosis / drug effects
  • Protein Transport / drug effects
  • Signal Transduction / drug effects
  • Xenograft Model Antitumor Assays
  • bcl-2-Associated X Protein / metabolism


  • Antineoplastic Agents
  • Diterpenes
  • bcl-2-Associated X Protein
  • eupalmerin acetate
  • JNK Mitogen-Activated Protein Kinases