frondoside-a and Leukemia

Acute leukemia is the major cause of mortality in hematological malignancies. Despite improvement of survival with current chemotherapies, patients die from the disease or side-effects of treatment. Thus, new therapeutic agents are needed. Frondoside A is a triterpenoid glycoside originally isolated from the sea cucumber, Cucumaria frondosa that has potent antitumor effects in various cancers. The current study investigated the effects of frondoside A in acute leukemia cell lines alone and in combination with drugs used for this malignancy. This study is the first comparing the efficacy of frondoside A to available conventional drugs. The acute leukemia cell lines used were CCRF-CEM, HL-60 and THP-1. Cells were cultured and treated with different concentrations of vincristine sulphate, asparaginase and prednisolone alone and in combination with frondoside A. The inhibitory concentration 50 (IC

Topics: Acute Disease; Animals; Antineoplastic Agents; Apoptosis; Cell Proliferation; Drug Synergism; Glycosides; Humans; Leukemia; Sea Cucumbers; Triterpenes; Tumor Cells, Cultured

Frondoside A is a pentaoside having an acetyl moiety at the aglycon ring and xylose as a third monosaccharide residue. Cucumarioside A(2)-2 is a pentaoside having glucose as a third monosaccahride unit. We compared the effects of frondoside A and A(2)-2 for cell death-inducing capability with close attention paid to structure-activity relationships. Both frondoside A and A(2)-2 strongly induced apoptosis of leukemic cells. Frondoside A-induced apoptosis was more potent and rapid than A(2)-2-induced apoptosis. A(2)-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.

Topics: Animals; Annexin A5; Apoptosis; Caspases; Cell Survival; Dose-Response Relationship, Drug; Enzyme Activation; Fluorescein-5-isothiocyanate; Fluorescent Dyes; Glycosides; HL-60 Cells; Humans; Lethal Dose 50; Leukemia; Molecular Structure; Saponins; Sea Cucumbers; Time Factors; Triterpenes