title: Apoptosis of K562 leukemia cells by Abnobaviscum F®, a European mistletoe             extract.
abstract: Evidence suggests that mistletoe extract has the potential to be used as             an anticancer agent. Abnobaviscum F® is a European mistletoe extract from the             host tree Fraxinus. We investigated the effect of Abnobaviscum F on the growth             and survival of different leukemia cell lines. Abnobaviscum F treatment strongly             reduced survival and induced apoptosis of K562 (human myeloid leukemia), RPMI-8226             (human plasmacytoma) and L1210 (murine lymphocytic leukemia) cells in culture.             Using K562 cells to further investigate the mechanism of action of Abnobaviscum F,             we showed that Abnobaviscum F-induced cell death was associated with the activation             of caspase-9, JNK-1/2 and p38 MAPK, as well as with the downregulation of Mcl-1,             and inhibition of ERK-1/2 and PKB phosphorylation. Moreover, Abnobaviscum F treatment             led to both a reduction of cellular glutathione (GSH) and the induction of ER             stress (GRP78 and CHOP induction and eIF-2α phosphorylation). By contrast, Abnobaviscum F             did not impact the expression of the DR4 and DR5 death receptors. The Abnobaviscum F-induced             apoptosis of K562 cells was blocked by pretreatment with either GSH, z-VAD-fmk             or SP600125. Our results, therefore, show that Abnobaviscum F induces apoptosis             of K562 cells through the activation of the intrinsic caspase pathway, the phosphorylation             of JNK-1, the reduction of cellular GSH, and the induction of ER stress.
authors.affiliation: Department of Medical Genetic Engineering, School of Medicine, Keimyung University, Dalseo-Gu, Daegu 704-701, Republic of Korea.
authors.forename: Yu-Kyoung
authors.initials: YK
authors.lastname: Park
authors.forename: Young Rok
authors.initials: YR
authors.lastname: Do
authors.forename: Byeong-Churl
authors.initials: BC
authors.lastname: Jang
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D053453:Caspase 9 / Q000096:biosynthesis / Q000378:metabolism; D045744:Cell Line, Tumor; D053938:DNA Fragmentation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000096:biosynthesis; D005978:Glutathione / Q000378:metabolism / Q000494:pharmacology; D006360:Heat-Shock Proteins / Q000096:biosynthesis; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020014:K562 Cells; D007945:Leukemia, Lymphoid / Q000378:metabolism / Q000473:pathology*; D007951:Leukemia, Myeloid / Q000378:metabolism*; D051379:Mice; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D010954:Plasmacytoma / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000096:biosynthesis; D051742:Transcription Factor CHOP / Q000096:biosynthesis; D028182:Viscum album / Q000737:chemistry*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D000873:Anthracenes; C497249:DDIT3 protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; D015852:Eukaryotic Initiation Factor-2; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; C579094:Mcl1 protein, mouse; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D051742:Transcription Factor CHOP; C432165:pyrazolanthrone; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D053453:Caspase 9; D005978:Glutathione