| Literature DB >> 16356849 |
Lan Chun Tu1, Chien-Shu Chen, I-Ching Hsiao, Ji-Wang Chern, Chi-Hung Lin, Ya-Ching Shen, Sheau Farn Yeh.
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.Entities:
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Year: 2005 PMID： 16356849 DOI： 10.1016/j.chembiol.2005.09.014
Source DB: PubMed Journal: Chem Biol ISSN： 1074-5521