title: Induction of microtubule-damage, mitotic arrest, Bcl-2 phosphorylation, Bak activation, and mitochondria-dependent caspase cascade is involved in human Jurkat T-cell apoptosis by aruncin B from Aruncus dioicus var. kamtschaticus.
abstract: Exposure of human Jurkat T cells to aruncin B, purified from Aruncus dioicus, caused apoptosis along with microtubule damage, G(2)/M-arrest, Bcl-2 phosphorylation, Bak activation, mitochondrial membrane potential (Δψm) loss, cytochrome c release, activation of multiple caspases, and PARP degradation. Analyses by employing Bcl-2 overexpression and selective caspase inhibitors revealed that G(2)/M-arrest and Bcl-2 phosphorylation occurred prior to mitochondria-dependent activation of caspase-9, -3, and -8. The IC(50) values for human resting T cells, activated T cells, and Jurkat T cells were >60μg/ml, 49μg/ml, and 22μg/ml, respectively. These results demonstrate the apoptogenic activity of a novel microtubule-damaging agent aruncin B.
authors.affiliation: Laboratory of Immunobiology, School of Life Science and Biotechnology, College of Natural Sciences, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Cho Rong
authors.initials: CR
authors.lastname: Han
authors.forename: Do Youn
authors.initials: do Y
authors.lastname: Jun
authors.forename: Hyun Ju
authors.initials: HJ
authors.lastname: Woo
authors.forename: Su-Yang
authors.initials: SY
authors.lastname: Jeong
authors.forename: Mi-Hee
authors.initials: MH
authors.lastname: Woo
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Kim
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D019169:Jurkat Cells / Q000187:drug effects / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008870:Microtubules / Q000187:drug effects*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011714:Pyrans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D027824:Rosaceae / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000378:metabolism
chemical_list: C574448:2-(8'-ethoxy-8'-methylpropylidene)-5-hydroxy-3,6-dihydro-2H-pyran-4-carboxylic acid; D000970:Antineoplastic Agents; D061945:Caspase Inhibitors; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D011714:Pyrans; D050998:bcl-2 Homologous Antagonist-Killer Protein; D020169:Caspases