The mitotic-arresting and apoptosis-inducing effects of diosgenyl saponins on human leukemia cell lines.
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 mitochondria-dependent 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.
Liu
Ming-Jie
MJ
Department of Biological Sciences and Biotechnology, Tsinghua University.
Wang
Zhao
Z
Ju
Yong
Y
Zhou
Jiang-bing
JB
Wang
Yu
Y
Wong
Ricky Ngok-Shun
RN
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000188:drug therapy* / Q000473:pathology; D008938:Mitosis / Q000187:drug effects / Q000502:physiology; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology; D012503:Saponins / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use
D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D012503:Saponins