title: Selective inhibition of bleomycin-induced G2 cell cycle checkpoint by simaomicin alpha.
abstract: Human T-cell leukemia-derived Jurkat cells are known to be defective in the G1 checkpoint. DNA-damaging agent bleomycin arrests the cell cycle at G2 phase of Jurkat cells, and microtubule-acting colchicine arrests it at the M phase. Simaomicin alpha, an actinomycete metabolite, itself showed no effect on the cell cycle status of Jurkat cells at least up to 6.0 nM. However, the compound (0.6-6.0 nM) was found to abrogate the bleomycin-induced G2 arrest, yielding a drastic decrease in cells at the G2 phase and increase in cells at the subG1 and G1 phases. On the other hand, the compound did not show any effect on the colchicine-induced M phase arrest in Jurkat cells. Furthermore, the compound showed almost no effect on the cell cycle status of the bleomycin-treated or -untreated normal cell line HUVEC. These data suggested that simaomicin alpha disrupts the cell cycle G2 checkpoint of cancer cells selectively, leading to sensitization of cancer cells to anti-cancer reagents.
authors.affiliation: Kitasato Institute for Life Sciences and Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Arai
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sato
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Masashi
authors.initials: M
authors.lastname: Suganuma
authors.forename: Takumi
authors.initials: T
authors.lastname: Kawabe
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tomoda
authors.forename: Satoshi
authors.initials: S
authors.lastname: Omura
mesh_terms: D001761:Bleomycin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D016195:G2 Phase / Q000187:drug effects*; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology*; D019169:Jurkat Cells
chemical_list: D007546:Isoquinolines; C066125:simaomicin alpha; D001761:Bleomycin