Targeting hr repair as a synthetic lethal approach to increase dna damage sensitivity by a rad52 inhibitor in brca2-deficient cancer cells

Wei Che Tseng, Chi Yuan Chen, Ching Yuh Chern, Chu An Wang, Wen Chih Lee, Ying Chih Chi, Shu Fang Cheng, Yi Tsen Kuo, Ya Chen Chiu, Shih Ting Tseng, Pei Ya Lin, Shou Jhen Liou, Yi Chen Li, Chin Chuan Chen

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

BRCA mutation, one of the most common types of mutations in breast and ovarian cancer, has been suggested to be synthetically lethal with depletion of RAD52. Pharmacologically inhibiting RAD52 specifically eradicates BRCA-deficient cancer cells. In this study, we demonstrated that curcumin, a plant polyphenol, sensitizes BRCA2-deficient cells to CPT-11 by impairing RAD52 recombinase in MCF7 cells. More specifically, in MCF7-siBRCA2 cells, curcumin reduced homologous recombination, resulting in tumor growth suppression. Furthermore, a BRCA2-deficient cell line, Capan1, became resistant to CPT-11 when BRCA2 was reintroduced. In vivo, xenograft model studies showed that curcumin combined with CPT-11 reduced the growth of BRCA2-knockout MCF7 tumors but not MCF7 tumors. In conclusion, our data indicate that curcumin, which has RAD52 inhibitor activity, is a promising candidate for sensitizing BRCA2-deficient cells to DNA damage-based cancer therapies.

Original languageEnglish
Article number4422
JournalInternational journal of molecular sciences
Volume22
Issue number9
DOIs
Publication statusPublished - 2021 May 1

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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