Methylanthraquinone from Hedyotis diffusa WILLD induces Ca(2+)-mediated apoptosis in human breast cancer cells.
Methylanthraquinone from Hedyotis diffusa WILLD exhibited potent anticancer activity in many kinds of cancer cells. However, the exact mechanism and signaling pathway involved in methylanthraquinone-induced apoptosis have not been fully elucidated. Therefore, we explored the mechanisms of methylanthraquinone-mediated apoptosis in MCF-7 human breast cancer cells. When MCF-7 cells were co-incubated with methylanthraquinone, the percentage of apoptotic cell and S phase of cell cycle was markedly increased. In addition, a rise in intracellular calcium levels, phosphorylation of JNK and activation of calpain were found in MCF-7 cells after exposure to methylanthraquinone. With the methylanthraquinone-mediated reduction of mitochondrial membrane potential, cytochrome c was released from mitochondria to cytosol. Moreover, methylanthraquinone strongly induced cleavage of caspase-4, caspase-9 and caspase-7 in MCF-7 cells. These results suggested that methylanthraquinone from Hedyotis diffusa WILLD induced MCF-7 cells apoptosis via Ca(2+)/calpain/caspase-4 pathway.
Liu
Zheng
Z
School of Life Sciences and Biopharmaceuticals, Shenyang Pharmaceutical University, Shenyang, China. liu306608@sohu.com.cn
Liu
Ming
M
Liu
Miao
M
Li
Jianchun
J
D000880:Anthraquinones / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002118:Calcium / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis; D005260:Female; D032064:Hedyotis / Q000737:chemistry*; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D051336:Mitochondrial Membranes / Q000187:drug effects
D000880:Anthraquinones; D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; D004273:DNA, Neoplasm; D053148:Caspase 3; D002118:Calcium