title: Role of calcium ion in induction of apoptosis by etoposide in human leukemia HL-60 cells.
abstract: The epipodophyllotoxin derivative etoposide, an inhibitor of DNA topoisomerase II, has been found to induce internucleosomal DNA fragmentation, characteristic of apoptosis. In the present study, we examined the effect of Ca2+ depletion on VP-16-induced endonucleolytic DNA cleavage in HL-60 cells. VP-16-induced internucleosomal DNA fragmentation could not be blocked by the extracellular Ca2+ chelator EGTA. However, an intracellular Ca2+ chelator BAPTA-AM, which was added after treatment with VP-16, abolished both internucleosomal DNA fragmentation and the morphologic features of apoptosis. No significant increase of intracellular Ca2+ was found after VP-16 treatment. We demonstrate for the first time that preexisting intracellular Ca2+ plays an essential role in induction of apoptosis by VP-16 in HL-60 cells.
authors.affiliation: First Department of Internal Medicine, Fukui Medical School, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Yoshida
authors.forename: T
authors.initials: T
authors.lastname: Ueda
authors.forename: R
authors.initials: R
authors.lastname: Takauji
authors.forename: Y P
authors.initials: YP
authors.lastname: Liu
authors.forename: T
authors.initials: T
authors.lastname: Fukushima
authors.forename: M
authors.initials: M
authors.lastname: Inuzuka
authors.forename: T
authors.initials: T
authors.lastname: Nakamura
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D002614:Chelating Agents / Q000494:pharmacology*; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000187:drug effects* / Q000302:isolation & purification; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005047:Etoposide / Q000633:toxicity*; D005456:Fluorescent Dyes; D016257:Fura-2 / Q000031:analogs & derivatives; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute; D014407:Tumor Cells, Cultured
chemical_list: D002614:Chelating Agents; D004273:DNA, Neoplasm; D005456:Fluorescent Dyes; C049925:fura-2-am; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; D005047:Etoposide; D002118:Calcium; D016257:Fura-2