Tanshinone I suppresses hepatocellular carcinoma cells growth through targeting DNA double-strand break repair

Zhen Qian; Nannan Feng; Anke Geng

doi:10.1080/15384047.2023.2229958

Tanshinone I suppresses hepatocellular carcinoma cells growth through targeting DNA double-strand break repair

Cancer Biol Ther. 2023 Dec 31;24(1):2229958. doi: 10.1080/15384047.2023.2229958.

Authors

Zhen Qian^{1

2}, Nannan Feng¹, Anke Geng²

Affiliations

¹ School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.

Abstract

Hepatocellular carcinoma (HCC) is one of the most common types of malignant tumors with increasing incidence rates and high mortality rates. The currently available methods for treating HCC include surgery, radiotherapy or chemotherapy, but all of them have limitations. Therefore, developing novel therapeutic methods for HCC is in great need. Here, in this study, we found that tanshinone I, a small molecule compound, inhibited the proliferation of HCC cells in a dose-dependent manner. We also observed that Tanshinone I destabilized genomes by inhibiting both NHEJ and HR repair pathways, which are responsible for repairing DNA double strand breaks (DSBs). Mechanistically, this compound suppressed the expression of 53BP1, and the recruitment of RPA2 to DNA damage sites. Importantly, we demonstrated that combining Tanshinone I with radiotherapy exhibited better therapeutic potential for treating HCC.

Keywords: Double strand break repair; Hepatocellular carcinoma (HCC); Homologous recombination; Non-homologous end joining; Tanshinone I.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Hepatocellular* / drug therapy
Carcinoma, Hepatocellular* / genetics
DNA / metabolism
DNA / therapeutic use
DNA Breaks, Double-Stranded
DNA End-Joining Repair
DNA Repair
Humans
Liver Neoplasms* / drug therapy
Liver Neoplasms* / genetics
Recombinational DNA Repair

Substances

tanshinone
DNA

Grants and funding

The work was supported by grants from the National Natural Science Foundation of China (Grant Nos. 32100605) and the Shanghai Sailing Program (Shanghai Sailing Program 21YF1436000)