Deep learning-assisted high-content screening identifies isoliquiritigenin as an inhibitor of DNA double-strand breaks for preventing doxorubicin-induced cardiotoxicity.

Journal: Biology direct
PMID:

Abstract

BACKGROUND: Anthracyclines including doxorubicin are essential components of many cancer chemotherapy regimens, but their cardiotoxicity severely limits their use. New strategies for treating anthracycline-induced cardiotoxicity (AIC) are still needed. Anthracycline-induced DNA double-strand break (DSB) is the major cause of its cardiotoxicity. However, DSB-based drug screening for AIC has not been performed possibly due to the limited throughput of common assays for detecting DSB. To discover new therapeutic candidates for AIC, here we established a method to rapidly visualize and accurately evaluate the intranuclear anthracycline-induced DSB, and performed a screening for DSB inhibitors.

Authors

  • Xuechun Chen
    Department of Cardiology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China.
  • Changtong Liu
    College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Xihu District, Hangzhou, 310058, China.
  • Hong Zhao
    Key Laboratory of Medical Image Computing of Ministry of Education, Northeastern University, Shenyang, China.
  • Yigang Zhong
    Department of Cardiology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China.
  • Yizhou Xu
    Department of Cardiology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China. qqyzxu@hotmail.com.
  • Yi Wang
    Department of Neurology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.