A Comparative Study of Marine Saponins from Sea Cucumbers as Potent Cytotoxic Agents Against Aggressive Human Cancer Cell Lines

Cancer remains a global health challenge, particularly esophageal squamous cell carcinoma and hepatocellular carcinoma, which have limited effective therapies and poor survival outcomes. Marine organisms, especially sea cucumbers, have historically been recognized in traditional medicine and represent an invaluable source of novel bioactive compounds. Saponins, the triterpenoid secondary metabolites abundant in sea cucumbers, are emerging as potential cytotoxic agents. In this study, we conducted a detailed comparative analysis of saponin profiles from eight geographically diverse sea cucumber species, identifying profound species-specific cytotoxic effects. Among these, saponins from Astichopus multifidus (Sluiter, 1910), Stichopodidae (sample-C) exhibited outstanding potency, significantly surpassing the effectiveness of conventional chemotherapy drugs, cisplatin and 5-fluorouracil. We purified and structurally characterized a putative triterpenoid saponin from this species, with the structure tentatively assigned on the basis of LC–MS, FT-IR and ¹H-NMR data, confirming its ability to induce apoptosis selectively in hepatocellular carcinoma cells via PARP-1 cleavage. These findings establish sea cucumber-derived saponins as promising cytotoxic candidates warranting further clinical investigation. © The Author(s) 2026.