Flor et al., Top1-HNE, 2020

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Data related to 2020 manuscript by Flor et. al submitted to Cell Chemical Biology. Data supports hypothesis that Top1-targeting chemotherapeutic poisons induce off-target effects in tumor cells by generating reactive oxygen species (ROS). ROS production results in lipid peroxidation (LPO) and subsequent generation of lipid-derived electrophiles (LDEs) including 4-hydroxy-2-nonenal (HNE). We show that HNE and other LDEs are able to post-translationally modify topoisomerase 1, inhibit its enzymatic activity, and induce Top1-DNA covalent complexes in tumor cells. Also discussed are cellular effects of Top1 inhibition by various Top1 poisons including accelerated senescence in tumor cells, which may be mediated by Top1-HNE adduct formation.

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