The Mitotic-Arresting and Apoptosis-Inducing Effects of Diosgenyl Saponins on Human Leukemia Cell Lines(Pharmacology)

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Diosgenyl saponins are the most abundant steroid saponins, and exert a large variety of biological functions. In a previous report, we showed that dioscin was able to induce cytotoxicity and apoptosis in human myeloblast leukemia HL-60 cells. This study further investigated the action mechanisms underlying this effect. The activation of caspase-9 and -3, but not caspase-8, together with the down-regulation of anti-apoptotic Bcl-2 protein, demonstrated that the apoptotic signaling triggered by dioscin was mediated through the intrinsic mitochondriadependent pathway. We also investigated its anti-proliferative effect on human chronic myelogenous leukemia K562 cells. Flow cytometry analysis showed that dioscin treatment induced the accumulation of cells in the G_2/M phase. Cytomorphology with DAPI and Wright-Giemsa staining demonstrated the enlargement of cell volume and multinucleation in the treated cells. Subsequent apoptosis was delineated with phosphatidylserine externalization and DNA hypodiploidy. Trillin was one of the hydrolysates of dioscin. We demonstrated that it could induce multinucleation in HL-60, K562 and human promyelocytic leukemia NB_4 cells, suggesting its extensive mitotic-arresting effects. As the diosgenyl sapogenin, diosgenin was also shown to be able to induce multinucleation and apoptosis in K562 cells in a similar manner to dioscin. These findings suggest that diosgenyl saponins have the properties to induce mitotic arrest and apoptosis, suggesting that they may be a new kind of antimitotic agent.
公益社団法人日本薬学会の論文
2004-07-01

The Mitotic-Arresting and Apoptosis-Inducing Effects of Diosgenyl Saponins on Human Leukemia Cell Lines(Pharmacology)

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