title: Aphidicolin potentiates apoptosis induced by arabinosyl nucleosides in human myeloid leukemia cell lines.
abstract: We investigated the effect of aphidicolin, an inhibitor of DNA polymerase alpha and delta, on the induction of apoptosis by arabinosyl nucleosides in a human promyelocytic leukemia cell line, HL-60. Pretreatment of HL-60 cells with aphidicolin (2 microM) significantly increased the number of morphologically apoptotic cells induced by 1-beta-D arabinofuranosylcytosine (ara-C) during 4 hr of incubation. This is consistent with the appearance of DNA fragmentation as determined quantitatively by diphenylamine or by agarose gel electrophoresis. The inhibition of cell growth on day 3 after drug exposure was correlated with the degree of apoptosis: Such synergistic interaction between aphidicolin and ara-C has also been observed in other human myeloid leukemia cell lines, U937 and KG-1. In addition, the induction of apoptosis by 9-beta-D arabinofuranosyladenine or 9-beta-D arabinofuranosylguanine is augmented by aphidicolin.
authors.affiliation: Department of Pediatrics, Kyoto University, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kuwakado
authors.forename: M
authors.initials: M
authors.lastname: Kubota
authors.forename: H
authors.initials: H
authors.lastname: Hirota
authors.forename: S
authors.initials: S
authors.lastname: Adachi
authors.forename: K
authors.initials: K
authors.lastname: Matsubara
authors.forename: Y
authors.initials: Y
authors.lastname: Kasai
authors.forename: Y
authors.initials: Y
authors.lastname: Akiyama
authors.forename: H
authors.initials: H
authors.lastname: Mikawa
mesh_terms: D016590:Aphidicolin / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001087:Arabinonucleosides / Q000096:biosynthesis / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D004357:Drug Synergism; D004587:Electrophoresis, Agar Gel; D006801:Humans; D007951:Leukemia, Myeloid; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014740:Vidarabine / Q000494:pharmacology
chemical_list: D001087:Arabinonucleosides; D016590:Aphidicolin; D004247:DNA; D014740:Vidarabine