title: The beta-carboline analog Mana-Hox causes mitotic aberration by interacting with DNA.
abstract: Mana-Hox, an analog of beta-carbolines with anticancer activity, induces aberrant mitosis and delays mitotic exit. However, the cellular target is not known. In this study, we visualized the intracellular localization of Mana-Hox. Mana-Hox rapidly penetrated into cells (within 1 min) and concentrated on disorganized metaphase chromosomes after 13 hr of exposure. We demonstrated that Mana-Hox is a noncovalent DNA binder that can interact with DNA through intercalation and/or through minor groove binding. Furthermore, Mana-Hox also inhibits topoisomerase II relaxation activity in vitro, suggesting that Mana-Hox could perturb mitotic chromosome decatenation. Overall, Mana-Hox binding to DNA plays a critical role in the induction of aberrant mitosis and contributes to its anticancer activity.
authors.affiliation: Institute of Biochemistry and Molecular Biology, School of Life Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Lan Chun
authors.initials: LC
authors.lastname: Tu
authors.forename: Chien-Shu
authors.initials: CS
authors.lastname: Chen
authors.forename: I-Ching
authors.initials: IC
authors.lastname: Hsiao
authors.forename: Ji-Wang
authors.initials: JW
authors.lastname: Chern
authors.forename: Chi-Hung
authors.initials: CH
authors.lastname: Lin
authors.forename: Ya-Ching
authors.initials: YC
authors.lastname: Shen
authors.forename: Sheau Farn
authors.initials: SF
authors.lastname: Yeh
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D002243:Carbolines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D004247:DNA / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D004250:DNA Topoisomerases, Type II / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D007364:Intercalating Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D008938:Mitosis / Q000187:drug effects*; D008958:Models, Molecular; D015394:Molecular Structure; D059005:Topoisomerase II Inhibitors
chemical_list: D000970:Antineoplastic Agents; D002243:Carbolines; D007364:Intercalating Agents; C487937:Mana-Hox; D059005:Topoisomerase II Inhibitors; D004247:DNA; D004250:DNA Topoisomerases, Type II