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Abstract: Frondoside A is a pentaoside having an acetyl moiety at the aglycon ring and xylose as a third monosaccharide residue. Cucumarioside A2-2 is a pentaoside having glucose as a third monosaccahride unit. We compared the effects of frondoside A and A2-2 for cell death-inducing capability with close attention paid to structure–activity relationships. Both frondoside A and A2-2 strongly induced apoptosis of leukemic cells. Frondoside A-induced apoptosis was more potent and rapid than A2-2-induced apoptosis. A2-2-induced but not frondoside A-induced apoptosis was caspase-dependent. This suggests that holothurians may induce apoptosis of leukemic cells caspase-dependently or -independently, depending on the holothurian structure. [Copyright &y& Elsevier]