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 microM after 2 hr of incubation. We observed no blockage in G2/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 microM and 51 +/- 6 microM 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.

Matemone, a new bioactive bromine-containing oxindole alkaloid from the indian ocean sponge Iotrochota purpurea.

A new bioactive bromine-containing oxindole alkaloid, matemone (1), was isolated from the Indian Ocean sponge Iotrochota purpurea, together with the known 6-bromoindole-3-carbaldehyde. The structures were elucidated on the basis of spectral and chemical data. Compound 1 shows mild cytotoxicity against three cancer cell lines and marginal antibacterial activity against Staphyloccocus aureus. DNA intercalant screening demonstrated DNA interactions with 1. Both compounds inhibit division of sea-urchin eggs.

Caulerpenyne interferes with microtubule-dependent events during the first mitotic cycle of sea urchin eggs.

Caulerpenyne (Cyn), the major secondary metabolite synthesized by the green alga Caulerpa taxifolia proliferating in the Mediterranean Sea, is a cytotoxic sesquiterpene. As this compound has an antiproliferative potency by inhibiting division of many types of cells, we examined the precise effects of Cyn during the early development of the sea urchin Paracentrotus lividus. Whereas Cyn (60 microM) had no effect on fertilization, it blocked the first cell division in the same manner whether added before or after fertilization, provided the drug was added before or during metaphase. Immunofluorescence localization revealed that Cyn had no effect on the microtubular sperm aster formation, pronuclei migration and fusion, chromosome condensation, nuclear envelope breakdown, and bipolar mitotic spindle assembly. However, mitosis was blocked in a metaphase-like stage at which most chromosomes were aligned at the equatorial plate, while a few of them had not even migrated towards the metaphase plate. When added after the metaphase-anaphase transition, the first division occurred normally but the second division was inhibited with the same phenotype as described above. We previously showed that Cyn did not affect protein synthesis or H1 kinase activation or deactivation (Pesando et al., 1996, Aquat. Toxicol. 35, 139), but that it partially inhibited DNA synthesis. Our results establish that Cyn does not affect the microfilament-dependent processes of fertilization and cytokinesis and allows the beginning of mitosis, but prevents normal DNA replication and results in metaphase-like arrest of sea urchin embryos.

Evaluation of the toxicological risk to humans of caulerpenyne using human hematopoietic progenitors, melanocytes, and keratinocytes in culture.

The extensive growth of Caulerpa taxifolia in the Mediterranean sea produces important quantities of bioactive secondary metabolites unable to enter the food chain. The cytotoxic effects of caulerpenyne, the major secondary metabolite from C. taxifolia, was studied in different in vitro models: skin cells, primary cultures of melanocytes and keratinocytes, immortalized keratinocytes (HaCaT and HESV), and bone marrow cells (hematopoietic progenitors CFU-GM). Typical dose-response curves from neutral red uptake and MTT assays were recorded in all models with IC50 ranging from 6 to 24 microM. Hematopoietic progenitors were more sensitive to caulerpenyne than melanocyte and keratinocyte cell lines, which could be due to their higher proliferative rate. The distribution of aggregates in colonies, macroclusters, and microclusters of hematopoietic progenitors was also altered in the presence of caulerpenyne. From our evaluation of the caulerpenyne concentrations required to result in cellular toxicity, the risks of cutaneous and/or food intoxication to humans may be considered minimal.

Zarzissine, a new cytotoxic guanidine alkaloid from the Mediterranean sponge Anchinoe paupertas.

From a CH2Cl2 extract of the Mediterranean sponge Anchinoe paupertas were isolated and characterized zarzissine [2], a new 4,5-guanidino-pyridazine compound and the known p-hydroxybenzaldehyde [1]. The structure of zarzissine [2] was elucidated by spectroscopic methods, including the application of a number of 2D nmr techniques. Biological activities of compounds 1 and 2 were also determined, with zarzissine exhibiting cytotoxicity against three human and murine tumor cell lines.

Isolation, structural identification and biological activity of two metabolites produced by Penicillium olsonii Bainier and Sartory.

From the culture broth of a fungus, two metabolites have been isolated: bis(2-ethylhexyl)phthalate (DEHP) precedently isolated from Streptomyces sp. and 2-(4-hydroxyphenyl)-2-oxoacetaldehyde oxime (PHBA) here reported as a natural compound in the (E)-s-cis configuration. The producing organism was identified as a strain of Penicillium olsonii. Culture growth and chemical identification are discussed in the present work.

Traditional remedies used in the western Pacific for the treatment of ciguatera poisoning.

Ciguatera is a specific type of food poisoning associated with the ingestion of tropical fish, which, although normally safe for consumption, may at times contain high amounts of ciguatoxin, as well as other chemically related toxins. Widespread in tropical regions where coral reefs are present, ciguatera fish poisoning constitutes a major hindrance for local fishing industries, local economies and foreign trade. Because no symptomatic treatment has been totally satisfactory, folk remedies remain of great interest. In this paper, a list of plants used in treating ciguatera poisoning in the Western Pacific region is presented, with emphasis on species whose exact utilization (part of plant used, preparation, dosage) has been determined.