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• W3208981630 endingPage "105927" @default.
• W3208981630 startingPage "105927" @default.
• W3208981630 abstract "DNA topoisomerases are proved cancer therapeutic targets with clinically successful anticancer drugs for decades. However, the role of RNA topoisomerase (TOP3β) remained mysterious especially in cancer, and no targeted agent has been reported yet. In a target identification assay of anti-cancer compound using a modified DrugTargetSeqR strategy, mutation of TOP3B was detected in cancer cells acquired resistance to cinobufagin (CBG), a key compound of Huachansu that has been approved for cancer therapy in China. We demonstrated that CBG directly engaged with TOP3β, and promoted TOP3β depletion in wildtype but not mutant cancer cells. Notably, knockout of TOP3β in cancer cells significantly reduced tumor enlargement but not initiation, and inhibited colony formation upon nutrient deprivation. We also demonstrated that CBG induced formation of stress granule, RNA-loop and asymmetric DNA damages in cancer cells, and all these phenotypes were significantly attenuated in TOP3B knockout cells. Of note, examination of a panel of cancer cell lines revealed associations among cell growth inhibition and induction of DNA damage as well as TOP3B depletion upon CBG treatment. Our findings not only highlighted TOP3β as a promising therapeutic target of cancer, but also identified CBG as a lead chemical inhibitor of TOP3β for cancer therapy." @default.
• W3208981630 created "2021-11-08" @default.
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• W3208981630 date "2021-12-01" @default.
• W3208981630 modified "2023-10-18" @default.
• W3208981630 title "Small molecule targeting topoisomerase 3β for cancer therapy" @default.
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• W3208981630 doi "https://doi.org/10.1016/j.phrs.2021.105927" @default.
• W3208981630 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34740818" @default.
• W3208981630 hasPublicationYear "2021" @default.
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