Introduction ! Sea cucumbers are soft-bodied worm-like echinoderms and belong to the class Holothuroidea, which has 25 families, including about 200 genera with more than 1400 species [1] . Sea cucumbers have economic importance in Asian countries, especially in China where some sea cucumbers are used in traditional medicine [2] and are also perceived as a delicacy. In recent decades, sea cucumbers have gained great attention among researchers around the world, not only due to their nutritive

more »

... lue, but also for their potential health benefits and therapeutic uses [3] . A number of biological activities including anticancer, antiangiogenic, anticoagulant, antihypertension, and anti-inflammatory effects are ascribed to various species of sea cucumbers. Different classes of compounds such as triterpenoid glycosides (saponins), sulfated polysaccharides, glycosaminoglycan, sterols, phenolics, lectins, peptides, glycosphingolipids, and fatty acids were found to be present in sea cu-cumbers [3] . To date, more than 100 triterpenoid glycosides with widely studied anticancer and antiviral activities have been isolated and identified from sea cucumbers [1]. Holothuria moebii Ludwig is a species of sea cucumbers of the Holothuriidae family. Members of this species are always found under rocks near the ebb tide line and distributed mainly in the seas of Mauritius, Seychelles, Sri Lanka, South Japan, South China, Philippines, Indonesia, South Pacific, and North Austria [2] . Until now, there have been no reports on the constituents or medicinal uses of this species. As a part of our ongoing project for the discovery of novel antitumor agents from natural resources [4-7], we have conducted chemical studies on a methanol extract prepared from the whole bodies of H. moebii and investigated the bioactivity of the isolated compounds. Four sulfated saponins, 1-4 (l " Fig. 1) , were isolated from sea cucumber H. moebii. Alkaline hydrolysis of saponin 3, the major compound in the crude saponins, produced desulfated saponin 3B with an unusual modified xylose. Compound 2 is a new triterpenoid glycoside and 3B is a new artificial compound. We report herein the isolation Abstract ! The bioactive ingredients of sea cucumber Holothuria moebii were investigated, and four sulfated saponins (1-4) and one desulfated saponin (3B) with an unusual 3,4-epoxy xylose were obtained from this study. Compound 2 is a new triterpenoid saponin and 3B is a new artificial compound. On the basis of the extensive NMR and HRESIMS data, their structures were assigned as 3-O-[β-Dquinovopyranosyl-(1 → 2)-4-sodium sulfato-β-Dxylopyranosyl]-25-acetoxy-22-oxo-9(11)-holostene-3β,12α,17α-triol (2) and 3-O-[β-D-quinovopyranosyl-(1 → 2)-3,4-epoxy-β-xylopyranosyl]-22,25-epoxy-9(11)-holostene-3β,12α,17α-triol (3B). Compounds 1-4 showed activity suppressing the proliferation of four different glioma cells with IC 50 values ranging from 0.99 to 8.64 µM. New saponin 2 significantly induced apoptosis in human glioblastoma U87-MG cells and reduced the expression levels of several glioma metabolic enzymes of glycolysis and glutaminolysis. This study reveals for the first time that selectively targeting multiple glioma metabolic regulators of glycolysis and glutaminolysis might be one of the anti-glioma mechanisms of saponin 2. Supporting information available online at