title: Marine bromophenol bis(2,3-dibromo-4,5-dihydroxybenzyl) ether, induces mitochondrial apoptosis in K562 cells and inhibits topoisomerase I in vitro.
abstract: Bis(2,3-dibromo-4,5-dihydroxybenzyl) ether (BDDE) is a marine bromophenol compound derived from marine algae. Previous reports have shown that BDDE possesses cytotoxic activity. However, the mechanisms of its apoptotic activity as well as its potential cellular targets remain unclear. The present study demonstrated that BDDE displays broad-spectrum in vitro anticancer capabilities and exhibits potent apoptotic activity in K562 cells via mitochondrial pathway. Further study revealed that BDDE inhibits the activity of topoisomerase I but does not stimulate the formation of topoisomerase I-DNA complex nor intercalate into DNA. Ethidium bromide displacement fluorescence assay and molecular modeling results showed that BDDE mainly targets DNA and binds to DNA minor groove, and thereafter inhibits the activity of topoisomerase I. The results of this study indicated that BDDE, which has unique chemical structure different from current topoisomerase I inhibitors, could serve as a lead template for rational drug design and for future anticancer agents development.
authors.affiliation: Institute of Oceanology, Chinese Academy of Science, 7 Nanhai Rd, Qingdao 266071, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Jianteng
authors.initials: J
authors.lastname: Wei
authors.forename: Lin
authors.initials: L
authors.lastname: Qiu
authors.forename: Xiukun
authors.initials: X
authors.lastname: Lin
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D059447:Cell Cycle Checkpoints / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D004987:Ethers / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D020014:K562 Cells; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008958:Models, Molecular; D010636:Phenols / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D059004:Topoisomerase I Inhibitors / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D004987:Ethers; D010636:Phenols; D017382:Reactive Oxygen Species; D059004:Topoisomerase I Inhibitors; D004264:DNA Topoisomerases, Type I