Prostaglandins from a zoanthid: paclitaxel-like neurite-degenerating and microtubule-stabilizating activities

Two prostaglandins, PGA2 and PGB2, were isolated from the Okinawan zoanthid, Palythoa kochii, during a search for paclitaxel-like neurite-degenerating compounds from natural sources using a cell-based assay method. In the presence of PGA2 at 30 microM, the neuronal processes induced in PC12 cells by the nerve growth factor (NGF) degenerated over 24 h, whereas PGB2 had no effect on the neuronal processes of PC12 cells. This activity of PGA2 was similar to that of the microtubule-stabilizing agents, paclitaxel (Taxol) and epothilone A, unlike the microtubule-depolymerizing agent, colchicine, which brought about quick neurite degeneration within 3 h. PGA2 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.