Methyl protodioscin induces G(2)/M arrest and apoptosis in K562 cells with the hyperpolarization of mitochondria.

Posted by rob on May 27, 2005 under Uncategorized | Be the First to Comment

Liu MJ, Yue PY, Wang Z, Wong RN

Cancer Lett. 2005 Jun 28; 224(2): 229-41

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 G(2)/M arrest, with the appearance of polyploidy population. The levels of cyclin B1 decreased, whereas Cdc2 kept at a steady level. Subsequent apoptosis after G(2)/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 Ca(2+) 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 G(2)/M arrest and apoptosis, with mitochondrial hyperpolarization and the disruption of Ca(2+) homeostasis playing important roles.

Methyl protodioscin induces G(2)/M arrest and apoptosis in K562 cells with the hyperpolarization of mitochondria.