Cancer chemotherapeutic agents such as doxorubicin are DNA damage inducers that also kill normal cells, making them highly toxic to cancer patients. To improve the efficacy and safety of chemotherapy, it is important to develop new chemotherapeutic agents that selectively kill cancer cells. Here we demonstrate that artemisitene (ATT), a natural derivative of the antimalarial drug artemisinin, selectively induces DNA double-stranded breaks (DSBs) and apoptosis in various human cancer cells by suppressing the expression of topoisomerases in human cancer cells. ATT effectively kills human cancer cells without apparent cytotoxicity on normal human cells or mouse liver and kidney. We discovered that c-Myc induces the expression of topoisomerases to prevent accumulation of DNA damage in human cancer cells. ATT selectively destabilizes c-Myc in human cancer cells by promoting the ubiquitination of c-Myc through the specific induction of the c-Myc E3 ligase NEDD4. Therefore, ATT represents a promising new chemotherapeutic drug candidate that can eliminate human cancer cells with minimized cytotoxic effects on normal cells.

中文翻译：

---

青蒿素通过解除对 c-Myc-拓扑异构酶途径的调节诱导 DNA 损伤来抑制肿瘤发生。

阿霉素等癌症化学治疗剂是 DNA 损伤诱导剂，也会杀死正常细胞，使它们对癌症患者具有高毒性。为了提高化疗的疗效和安全性，开发新的选择性杀死癌细胞的化疗药物非常重要。在这里，我们证明青蒿素 (ATT) 是抗疟药物青蒿素的一种天然衍生物，通过抑制人类癌细胞中拓扑异构酶的表达，选择性地诱导各种人类癌细胞的 DNA 双链断裂 (DSB) 和细胞凋亡。ATT有效杀死人类癌细胞，对正常人类细胞或小鼠肝脏和肾脏没有明显的细胞毒性。我们发现 c-Myc 诱导拓扑异构酶的表达以防止 DNA 损伤在人类癌细胞中的积累。ATT 通过特异性诱导 c-Myc E3 连接酶 NEDD4 促进 c-Myc 的泛素化，从而选择性地破坏人癌细胞中的 c-Myc。因此，ATT 代表了一种有前途的新型化疗药物候选者，它可以消除人类癌细胞，同时将对正常细胞的细胞毒性作用降至最低。