Differential effects of triterpene glycosides, frondoside A and cucumarioside A2‐2 isolated from sea cucumbers on caspase activation and apoptosis of human leukemia cells

• Published in: FEBS letters Vol. 583; no. 4; pp. 697 - 702
• Main Authors: Jin, Jun-O, Shastina, Valeria V., Shin, Sung-Won, Xu, Qi, Park, Joo-In, Rasskazov, Valery A., Avilov, Sergey A., Fedorov, Sergey N., Stonik, Valentin A., Kwak, Jong-Young
• Format: Journal Article
• Language: English
• Published: England 18.02.2009
• Subjects: 3,30-dihexyloxacarbocyanine iodide; AIF; Animals; Annexin A5 - metabolism; Apoptosis; Apoptosis - drug effects; apoptosis-inducing factor; Caspase; Caspases - metabolism; Cell Survival - drug effects; DiOC6; Dose-Response Relationship, Drug; endoplasmic reticulum; Enzyme Activation - drug effects; Fluorescein-5-isothiocyanate - metabolism; Fluorescent Dyes - metabolism; Frondoside A; Glycosides - chemistry; Glycosides - isolation & purification; Glycosides - pharmacology; HL-60 Cells; Humans; Lethal Dose 50; Leukemia; Leukemia - pathology; Molecular Structure; PARP; poly (ADP ribose) polymerase; Saponins - chemistry; Saponins - isolation & purification; Saponins - pharmacology; Sea Cucumbers - chemistry; Time Factors; Triterpene glycosides; Triterpenes - chemistry; Triterpenes - isolation & purification; Triterpenes - pharmacology
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2009.01.010

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.