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

Abstract

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.

• Authors: Arifumi Iwamaru, Eiji Iwado, Seiji Kondo, Robert A Newman, Burnilda Vera, Abimael D Rodríguez, Yasuko Kondo
• Journal: Molecular cancer therapeutics (Mol Cancer Ther) Vol. 6 Issue 1 Pg. 184-92 (Jan 2007) ISSN: 1535-7163 [Print] United States
• PMID: 17237278 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• Animals
• Anthozoa (chemistry)
• Antineoplastic Agents (chemistry, pharmacology)
• Apoptosis (drug effects)
• Caribbean Region
• Diterpenes (chemistry, pharmacology)
• Enzyme Activation (drug effects)
• Female
• G2 Phase (drug effects)
• Glioma (enzymology, metabolism, 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)