Marine bromophenol bis(2,3-dibromo-4,5-dihydroxybenzyl) ether, induces mitochondrial apoptosis in K562 cells and inhibits topoisomerase I in vitro

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.

► BDDE exhibits apoptotic activity in K562 cells via mitochondrial pathway.
► BDDE inhibits the activity of topoisomerase I.
► BDDE does not stimulate the formation of topoisomerase I–DNA complex.
► BDDE mainly targets DNA and binds to DNA minor groove.