title: Synergistic effect of 5-azacytidine and NF-κB inhibitor DHMEQ on apoptosis induction in myeloid leukemia cells.
abstract: Constitutive NF-κB activation characterizes a subset of myeloid leukemia (ML) cells. Recent reports have indicated that DNA methyltransferase (DNMT) inhibitors are alternative candidates for the treatment of ML. However, the optimal use of DNMT as a chemotherapeutic agent against ML has yet to be established. In this report, we examined the effect of the NF-κB inhibitor dehydroxymethylepoxyquinomicin (DHMEQ) and its combinational use with the DNMT inhibitor 5-azacytidine (AZA) in ML cell lines. DHMEQ alone induced cell death in ML cell lines with NF-κB activation, although the response varied among the cell lines. The addition of DHMEQ enhanced the effect of AZA on the viability and apoptosis induction of ML cell lines. The treatment of ML cell lines with AZA marginally induced NF-κB binding activity, although the treatment induced NF-κB protein. These results indicate the potential usefulness of DHMEQ and its combinational use with AZA in the treatment of ML, although the molecular effect by AZA on the NF-κB pathway awaits further study.
authors.affiliation: Department of Hematology, School of Medicine, Kitasato University, Minami-ku, Sagamihara, Kanagawa, Japan.
authors.forename: Tomiteru
authors.initials: T
authors.lastname: Togano
authors.forename: Makoto
authors.initials: M
authors.lastname: Nakashima
authors.forename: Mariko
authors.initials: M
authors.lastname: Watanabe
authors.forename: Kazuo
authors.initials: K
authors.lastname: Umezawa
authors.forename: Toshiki
authors.initials: T
authors.lastname: Watanabe
authors.forename: Masaaki
authors.initials: M
authors.lastname: Higashihara
authors.forename: Ryouichi
authors.initials: R
authors.lastname: Horie
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001374:Azacitidine / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003512:Cyclohexanones / Q000494:pharmacology*; D004357:Drug Synergism; D018922:HL-60 Cells; D006801:Humans; D020014:K562 Cells; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000473:pathology; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured
chemical_list: D001549:Benzamides; D003512:Cyclohexanones; D016328:NF-kappa B; C464444:dehydroxymethylepoxyquinomicin; D001374:Azacitidine