Caulerpenyne from Caulerpa taxifolia has an antiproliferative activity on tumor cell line SK-N-SH and modifies the microtubule network

Caulerpenyne, the major secondary metabolite synthesized by the green marine alga Caulerpa taxifolia, is cytotoxic against several cell lines. To identify possible targets of this toxin, we investigated the effect of caulerpenyne on the neuroblastoma SK-N-SH cell line. Caulerpenyne induced an inhibition of SK-N-SH cell proliferation with an IC50 of 10 +/- 2 muM after 2 hr of incubation. We observed no blockage in G(2)/M phase and an increase in cell death. On immunofluorescence microscopy, caulerpenyne affected the microtubule network in SK-N-SH cell line; we observed a loss of neurites and a compaction of the microtubule network at the cell periphery. In vitro, after 35 min of incubation, caulerpenyne inhibited the polymerization of pig brain purified tubulin or microtubule proteins, with an IC50 of 21 +/- 2 muM and 51 +/- 6 muM respectively. Analysis by electron microscopy indicated that caulerpenyne induced aggregation of tubulin, which may be responsible for inhibition of microtubule polymerization and bundling of residual microtubules. (C) 2001 Elsevier Science Inc. All rights reserved.