Constituents of the sea cucumber Cucumaria okhotensis. Structures of okhotosides B₁-B₃ and cytotoxic activities of some glycosides from this species

Three new triterpene oligoglycosides, okhotosides B₁ (1), B ₂ (2), and B₃ (3), have been isolated from the sea cucumber Cucumaria okhotensis along with the known compounds frondoside A (4), frondoside A₁, cucumarioside A₂-5, and koreoside A. The structures of 1-3 were elucidated on the basis of their spectroscopic data (2D NMR and MS). Compounds 1-3 were moderately toxic against HeLa tumor cells. Frondoside A (4) showed more potent cytotoxicity against THP-1 and HeLa tumor cell lines (with IC₅₀ values of 4.5 and 2.1 μg/mL, respectively) and decreased both the AP-1-dependent trascriptional activities induced by UVB, EGF, or TPA in JB6-LucAP-1 cells and the EGF-induced NF-κB-dependent transcriptional activity in JB6-LucNF-kB cells at doses of about 1 μg/mL. At the same doses, it increased the p53-dependent transcriptional activity in nonactivated JB6-Lucp53 cells and inhibited the colony formation of JB6 P ⁺ Cl 41 cells activated with EGF (INCC₅₀ = 0.8 μg/mL).