Prostaglandins from a Zoanthid : Paclitaxel-Like Neurite-Degenerating and Microtubule-Stabilizating Activities
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Two prostaglandins, PGA<SUB>2</SUB> and PGB<SUB>2</SUB>, were isolated from the Okinawan zoanthid, <I>Palythoa kochii</I>, during a search for paclitaxel-like neurite-degenerating compounds from natural sources using a cell-based assay method. In the presence of PGA<SUB>2</SUB> at 30 μ<small>M</small>, the neuronal processes induced in PC12 cells by the nerve growth factor (NGF) degenerated over 24 h, whereas PGB<SUB>2</SUB> had no effect on the neuronal processes of PC12 cells. This activity of PGA<SUB>2</SUB> was similar to that of the microtubule-stabilizing agents, paclitaxel (Taxol<SUP>®</SUP>) and epothilone A, unlike the microtubule-depolymerizing agent, colchicine, which brought about quick neurite degeneration within 3 h. PGA<SUB>2</SUB> stimulated tubulin polymerization, although less potently than paclitaxel. An examination of structure-activity relationships across several PGs suggests that the cyclopentenone ring structure and the orientation of its dipolar moment played an important role in the paclitaxel-like neurite-degenerating activity. These results suggest that the cyclopentenone-type PGs can interact with microtubules to inhibit their function like paclitaxel.
- Agricultural and Biological Chemistry
Agricultural and Biological Chemistry 70(3), 706-711, 2006-03-23
Japan Society for Bioscience, Biotechnology, and Agrochemistry