The β-carboline analog Mana-Hox causes mitotic aberration by interacting with DNA

Lan Chun Tu, Chien Shu Chen, I. Ching Hsiao, Ji Wang Chern, Chi Hung Lin, Ya Ching Shen, Sheau Farn Yeh*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Mana-Hox, an analog of β-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.

Original languageEnglish
Pages (from-to)1317-1324
Number of pages8
JournalChemistry and Biology
Volume12
Issue number12
DOIs
StatePublished - Dec 2005

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