title: Induction of apoptosis by ethanol extract of Prunus mume in U937 human leukemia cells through activation of caspases.
abstract: Prunus mume (P. mume), a traditional drug and health food in Korea, Japan and China, possesses various pharmacological activities that include a potential source of free radical scavenging, anti-viral, anti-microbial, anti-inflammatory and anti-cancer activities. However, the cellular and molecular mechanisms of apoptosis induction by P. mume in human cancer cells are poorly understood. In the present study, we conducted an investigation of the pro-apoptotic effects of an ethanol extract of P. mume (EEPM) in U937 human leukemia cells. Exposure to EEPM was found to result in a concentration-dependent growth inhibition by induction of apoptosis. Induction of apoptotic cell death of U937 cells by EEPM showed a correlation with the down-regulation of members of the inhibitor of apoptosis protein (IAP) family, including X-linked inhibitor of apoptosis protein (XIAP) and survivin, and anti-apoptotic Bcl-2, up-regulation of FasL, and cleavage of Bic. EEPM treatment induced proteolytic activation of caspase-3, -8 and -9, and degradation of caspase-3 substrate proteins, including poly(ADP-ribose) polymerase (PARP) and β-catenin. In addition, apoptotic cell death induced by EEPM was significantly inhibited by z-DEVD-fmk, a caspase-3-specific inhibitor, which demonstrated the important role played by caspase-3 in the process. Taken together, these findings suggest that EEPM may be a potential chemotherapeutic agent for use in the control of human leukemia U937 cells and that further studies are needed for the identification of the active compounds.
authors: Department of Biochemistry and Research Institute of Oriental Medicine, Dongeui University College of Oriental Medicine, Busan 614-052, Republic of Korea.
authors: Cheol
authors: C
authors: Park
authors: Cheng-Yun
authors: CY
authors: Jin
authors: Gi-Young
authors: GY
authors: Kim
authors: Yong Kee
authors: YK
authors: Jeong
authors: Wun-Jae
authors: WJ
authors: Kim
authors: Yung Hyun
authors: YH
authors: Choi
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D000431:Ethanol / Q000737:chemistry; D053222:Fas Ligand Protein / Q000378:metabolism; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D010936:Plant Extracts / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D027861:Prunus / Q000737:chemistry*; D020298:U937 Cells; D019014:fas Receptor / Q000378:metabolism
chemical_list: D061945:Caspase Inhibitors; D053222:Fas Ligand Protein; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor; D000431:Ethanol; D053148:Caspase 3; D020169:Caspases