Ginsenoside Rg1 impairs homologous recombination repair by targeting CtBP-interacting protein and sensitizes hepatoblastoma cells to DNA damage

The ginsenoside Rg1, the primary pharmacologically active ingredient of the traditional Chinese herb ginseng, is widely used in the clinical treatment of diseases of the immune and nervous systems. Recent studies have shown that it also has an antitumor effect. In this study, we explored the effects of Rg1 on hepatoblastoma (HB) and its underlying mechanisms. We demonstrated that Rg1 significantly inhibited HB cell growth both in vivo and in vitro. Mechanistic studies revealed that Rg1 impaired homologous recombination and triggered double-strand breaks in HB cells by directly targeting CtBP-interacting protein (CtIP), a key double-strand break repair factor, which is highly expressed in HB tissues. Moreover, we also demonstrated that Rg1 sensitized HB cells to DNA-damaging agents both in vitro and in vivo. In conclusion, our data not only demonstrate the potential clinical application of Rg1 as a novel chemotherapeutic candidate but also offer a mechanism-based therapeutic option by which DNA-damaging agents can be used in combination with Rg1 to target HB. *Ni Zhen and Lei Jin contributed equally to the writing of this article. Correspondence to Xiaorong Ni, PhD, Department of Gynecology, Shanghai Municipal Hospital of Traditional Chinese Medicine of Shanghai, University of Traditional Chinese Medicine, No. 274 Zhijiang Middle Road, Jingan District, 200071 Shanghai, People's Republic of China Tel: +86 216 258 8203; fax: +86 215 663 9828; e-mail: xiaorongni_stcmh00@163.com or Correspondence to Min Xu, PhD, Department of Surgery, Shanghai Children's Medical Center of Shanghai Jiaotong University School of Medicine, No. 1678 Dongfang Road, Pudong District, 200127 Shanghai, People's Republic of China Tel: +86 213 862 6161; fax: +86 215 089 1405; e-mail: xuminmed@163.com Received September 6, 2017 Accepted April 23, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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