Artesunate sensitizes ovarian cancer cells to cisplatin by downregulating RAD51

Bingliang Wang, Dong Hou, Qiao Liu, Tingting Wu, Haiyang Guo, Xiyu Zhang, Yongxin Zou, Zhaojian Liu, Jinsong Liu, Jianjun Wei, Yaoqin Gong, Changshun Shao

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29 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1548-1556
Number of pages9
JournalCancer Biology and Therapy
Volume16
Issue number10
DOIs
StatePublished - Oct 1 2015

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Keywords

  • RAD51
  • artesunate
  • chemosensitization
  • homologous recombination repair
  • ovarian cancer

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

Cite this

Wang, B., Hou, D., Liu, Q., Wu, T., Guo, H., Zhang, X., Zou, Y., Liu, Z., Liu, J., Wei, J., Gong, Y., & Shao, C. (2015). Artesunate sensitizes ovarian cancer cells to cisplatin by downregulating RAD51. Cancer Biology and Therapy, 16(10), 1548-1556. https://doi.org/10.1080/15384047.2015.1071738