title: Artesunate sensitizes ovarian cancer cells to cisplatin by downregulating RAD51.
abstract: Artesunate, a semi-synthetic derivative of arteminisin originally developed for the treatment of malaria, has recently been shown to possess antitumor properties. One of the cytotoxic effects of artesunate on cancer cells is mediated by induction of oxidative stress and DNA double-strand breaks (DSBs). We report here that in addition to inducing oxidative stress and DSBs, artesunate can also downregulate RAD51 and impair DSB repair in ovarian cancer cells. We observed that the formation of RAD51 foci and homologous recombination repair (HRR) were significantly reduced in artesunate-treated cells. As a consequence, artesunate and cisplatin synergistically induced DSBs and inhibited the clonogenic formation of ovarian cancer cells. Ectopic expression of RAD51 was able to rescue the increased chemosensitivity conferred by artesunate, confirming that the chemosensitizing effect of artesuante is at least partially mediated by the downregulation of RAD51. Our results indicated that artesunatecan compromise the repair of DSBs in ovarian cancer cells, and thus could be employed as a sensitizing agent in chemotherapy.
authors.affiliation: a Key Laboratory of Experimental Teratology Ministry of Education ; Department of Molecular Medicine and Genetics; Shandong University School of Medicine Jinan ; Shandong , China.
authors.forename: Bingliang
authors.initials: B
authors.lastname: Wang
authors.affiliation: a Key Laboratory of Experimental Teratology Ministry of Education ; Department of Molecular Medicine and Genetics; Shandong University School of Medicine Jinan ; Shandong , China.
authors.forename: Dong
authors.initials: D
authors.lastname: Hou
authors.affiliation: a Key Laboratory of Experimental Teratology Ministry of Education ; Department of Molecular Medicine and Genetics; Shandong University School of Medicine Jinan ; Shandong , China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Liu
authors.affiliation: a Key Laboratory of Experimental Teratology Ministry of Education ; Department of Molecular Medicine and Genetics; Shandong University School of Medicine Jinan ; Shandong , China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Wu
authors.affiliation: a Key Laboratory of Experimental Teratology Ministry of Education ; Department of Molecular Medicine and Genetics; Shandong University School of Medicine Jinan ; Shandong , China.
authors.forename: Haiyang
authors.initials: H
authors.lastname: Guo
authors.affiliation: a Key Laboratory of Experimental Teratology Ministry of Education ; Department of Molecular Medicine and Genetics; Shandong University School of Medicine Jinan ; Shandong , China.
authors.forename: Xiyu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: a Key Laboratory of Experimental Teratology Ministry of Education ; Department of Molecular Medicine and Genetics; Shandong University School of Medicine Jinan ; Shandong , China.
authors.forename: Yongxin
authors.initials: Y
authors.lastname: Zou
authors.affiliation: b Department of Cell Biology ; Shandong University School of Medicine Jinan ; Shandong , China.
authors.forename: Zhaojian
authors.initials: Z
authors.lastname: Liu
authors.affiliation: c Department of Pathology ; The University of Texas MD Anderson Cancer Center , Houston , TX USA.
authors.forename: Jinsong
authors.initials: J
authors.lastname: Liu
authors.affiliation: d Department of Pathology ; Northwestern University School of Medicine ; Chicago , IL USA.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Wei
authors.affiliation: a Key Laboratory of Experimental Teratology Ministry of Education ; Department of Molecular Medicine and Genetics; Shandong University School of Medicine Jinan ; Shandong , China.
authors.forename: Yaoqin
authors.initials: Y
authors.lastname: Gong
authors.affiliation: a Key Laboratory of Experimental Teratology Ministry of Education ; Department of Molecular Medicine and Genetics; Shandong University School of Medicine Jinan ; Shandong , China.|e Department of Genetics/Human Genetics Institute of New Jersey ; Rutgers University ; Piscataway , NJ USA.
authors.forename: Changshun
authors.initials: C
authors.lastname: Shao
mesh_terms: D000818:Animals; D037621:Artemisinins / Q000008:administration & dosage / Q000627:therapeutic use*; D000077332:Artesunate; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology; D015536:Down-Regulation; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D051135:Rad51 Recombinase / Q000235:genetics*; D017382:Reactive Oxygen Species
chemical_list: D037621:Artemisinins; D017382:Reactive Oxygen Species; D000077332:Artesunate; D051135:Rad51 Recombinase; D002945:Cisplatin
keywords: RAD51; artesunate; chemosensitization; homologous recombination repair; ovarian cancer