Journal
CANCER BIOLOGY & THERAPY
Volume 16, Issue 11, Pages 1585-1592Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/15384047.2015.1078021
Keywords
combination; DNA double strand break repair; Harmine; homologous recombination repair; Rad51
Categories
Funding
- Shanghai Municipal Natural Science Foundation [15ZR1442600]
- Cultural Program for Outstanding Young Talents in Tongji University
- National Science Foundation of China [81402543]
- China Postdoctoral Science Foundation [2014M551446]
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To avoid cell cycle arrest or apoptosis, rapidly proliferating cancer cells have to promote DNA double strand break (DSB) repair to fix replication stress induced DSBs. Therefore, developing drugs blocking homologous recombination (HR) and nonhomologous end joining (NHEJ) - 2 major DSB repair pathways - holds great potential for cancer therapy. Over the last few decades, much attention has been paid to explore drugs targeting DSB repair pathways for cancer therapy. Here, using 2 well-established reporters for analyzing HR and NHEJ efficiency, we found that both HR and NHEJ are elevated in hepatoma cell lines Hep3B and HuH7 compared with normal liver cell lines Chang liver and QSG-7701. Our further study found that Harmine, a natural compound, negatively regulates HR but not NHEJ by interfering Rad51 recruitment, resulting in severe cytotoxicity in hepatoma cells. Furthermore, NHEJ inhibitor Nu7441 markedly sensitizes Hep3B cells to the anti-proliferative effects of Harmine. Taken together, our study suggested that Harmine holds great promise as an oncologic drug and combination of Harmine with a NHEJ inhibitor might be an effective strategy for anti-cancer treatment.
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