title: Boromycin abrogates bleomycin-induced G2 checkpoint.
abstract: The DNA-damaging agent bleomycin arrests the cell cycle at the G2 phase of Jurkat cells defective in the G1 checkpoint, and microtubule-acting colchicine arrests it at the M phase. Boromycin itself, an actinomycete metabolite, showed no effect on the cell cycle status of Jurkat cells at least up to 340 nM. However, the compound (3.4-340 nM) was found to abrogate bleomycin-induced G2 arrest even at 3.4 nM, resulting in a drastic decrease in cells at the G2 phase and increase in cells at the subG1 phase. On the other hand, boromycin did not show any effect on the colchicine-induced M phase arrest in Jurkat cells, nor on the cell cycle status of the bleomycin-treated or -untreated HUVEC, normal cells conserving both G1 and G2 checkpoints. Furthermore, boromycin potentiated anti-tumor activity of bleomycin in scid mice inoculated with Jurkat cells. These data suggest that boromycin disrupts the cell cycle at the G2 checkpoint of cancer cells selectively, leading to sensitization of cancer cells to anti-cancer reagents.
authors.affiliation: Kitasato Institute for Life Sciences & 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: Yukio
authors.initials: Y
authors.lastname: Koizumi
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sato
authors.forename: Takumi
authors.initials: T
authors.lastname: Kawabe
authors.forename: Masashi
authors.initials: M
authors.lastname: Suganuma
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tomoda
authors.forename: Satoshi
authors.initials: S
authors.lastname: Omura
mesh_terms: D000818:Animals; D001761:Bleomycin / Q000494:pharmacology*; D001881:Borates / Q000494:pharmacology*; D016195:G2 Phase / Q000187:drug effects*; D006801:Humans; D019169:Jurkat Cells; D008297:Male; D051379:Mice; D016513:Mice, SCID
chemical_list: D001881:Borates; D001761:Bleomycin; C000302:boromycin