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Sulfated Glycosides from the Sea Cucumbers Block Ca2+ Flow in Murine Neuroblastoma Cells

Recently the ability of triterpene glycosides from sea cucumbers to interact with purinergic receptors of P2X family on the membranes of immune cells enhancing the reversible ATP-dependent Ca2+ intake and therefore modulating (stimulating) the receptor's activity was discovered. As a result the activation of cellular immunity on the organism level was observed. Purinergic receptors are associated with a series of important functions in normal and pathophysiology, thus the searching of its new modulators (both stimulants and blockers) seems to be very important medical and scientific task. The cytotoxic activity of four triterpene glycosides isolated from different species of sea cucumbers: liouvilloside A (1) from Pseudocolochirus violaceus, fallaxoside D1 (2) from Cucumaria fallax and magnumosides C3 (3) and C4 (4) from Massinium (=Neothynidium) magnum against neuroblastoma Neuro 2A cells was tested. The glycosides 1 and 4 were the most cytotoxic in the series (EC50 5.0 μM and 21.5 μM, correspondingly). Moreover, non-cytotoxic concentration (1 μM) of these compounds inhibited ATP-dependent Ca2+ intake into the Neuro 2A cells, containing P2X7 receptors on the surface, by 53 and 47%, correspondingly. The ability of sea cucumbers triterpene glycosides to block the purinergic receptors in vitro is first discovered.