Methyl protodioscin induces G2/M arrest and apoptosis in K562 cells with the hyperpolarization of mitochondria.
Methyl protodioscin is a furostanol bisglycoside with antitumor properties. The present study investigated its effects on human chronic myelogenous leukemia K562 cells. Cell cycle analysis showed that methyl protodioscin caused distinct G2/M arrest, with the appearance of polyploidy population. The levels of cyclin B1 decreased, whereas Cdc2 kept at a steady level. Subsequent apoptosis after G2/M blockage was demonstrated through DNA fragmentation and the annexin V staining assay. Methyl protodioscin induced a biphasic alteration (i.e. an early hyperpolarization, followed by depolarization) in mitochondrial membrane potential of K562 cells. The transient decline of intracellular Ca2+ concentration was observed at early stage. The generation of reactive oxygen species was also detected. The anti-apoptotic Bcl-x(L) transiently increased and then decreased. And the pro-apoptotic Bax was markedly up-regulated. Taken together, these data demonstrated that methyl protodioscin inhibits K562 cell proliferation via G2/M arrest and apoptosis, with mitochondrial hyperpolarization and the disruption of Ca2+ homeostasis playing important roles.
Liu
Ming-Jie
MJ
Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing, P.R. China.
Yue
Patrick Ying-Kit
PY
Wang
Zhao
Z
Wong
Ricky Ngok-Shun
RN
D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000493:pharmacokinetics; D002453:Cell Cycle / Q000187:drug effects*; D049109:Cell Proliferation; D004249:DNA Damage; D004144:Diosgenin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006706:Homeostasis; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology*; D008928:Mitochondria / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D012503:Saponins / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D012503:Saponins; D051028:bcl-2-Associated X Protein; C425324:methyl protodioscin; D004144:Diosgenin; D002118:Calcium