机构：[1]Guangdong Provincial Key Laboratory of Tumor Immunotherapy, Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China[2]Center for Regenerative and Translational Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510632, China广东省中医院[3]Division of Biological Sciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0322, USA
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.
基金：
Postdoctoral Science Foundation of ChinaChina Postdoctoral Science Foundation [2015M582371]; NSFCNational Natural Science Foundation of China [81430032, U1601222, 81502595]; Guangdong Provincial Key Laboratory of Cancer Immunotherapy; Guangzhou Key Laboratory of Tumor Immunology Research; Guangdong Provincial Key Special Science and Technology Project [2015B020225004]; Guangdong NSF Major basic research developmental project; California Institute for Regenerative MedicineCalifornia Institute for Regenerative Medicine
第一作者机构：[1]Guangdong Provincial Key Laboratory of Tumor Immunotherapy, Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
通讯作者：
通讯机构：[1]Guangdong Provincial Key Laboratory of Tumor Immunotherapy, Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China[2]Center for Regenerative and Translational Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510632, China[3]Division of Biological Sciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0322, USA
推荐引用方式(GB/T 7714)：
Chen Jian,Li Wenjuan,Cui Ke,et al.Artemisitene suppresses tumorigenesis by inducing DNA damage through deregulating c-Myc-topoisomerase pathway[J].ONCOGENE.2018,37(37):5079-5087.doi:10.1038/s41388-018-0331-z.
APA：
Chen, Jian,Li, Wenjuan,Cui, Ke,Ji, Kaiyuan,Xu, Shuxiang&Xu, Yang.(2018).Artemisitene suppresses tumorigenesis by inducing DNA damage through deregulating c-Myc-topoisomerase pathway.ONCOGENE,37,(37)
MLA：
Chen, Jian,et al."Artemisitene suppresses tumorigenesis by inducing DNA damage through deregulating c-Myc-topoisomerase pathway".ONCOGENE 37..37(2018):5079-5087
医学