Berberine attenuates XRCC1-mediated base excision repair and sensitizes breast cancer cells to the chemotherapeutic drugs

J Cell Mol Med. 2019 Oct;23(10):6797-6804. doi: 10.1111/jcmm.14560. Epub 2019 Jul 23.

Abstract

Berberine (BBR) is a natural isoquinoline alkaloid, which is used in traditional medicine for its anti-microbial, anti-protozoal, anti-diarrhoeal activities. Berberine interacts with DNA and displays anti-cancer activities, yet its effects on cellular DNA repair and on synthetic treatments with chemotherapeutic drugs remain unclear. In this study, we investigated the effects of BBR on DNA repair and on sensitization of breast cancer cells to different types of DNA damage anti-tumoural drugs. We found BBR arrested cells in the cell cycle S phase and induced DNA breaks. Cell growth analysis showed BBR sensitized MDA-MB-231 cells to cisplatin, camptothecin and methyl methanesulfonate; however, BBR had no synergistic effects with hydroxurea and olaparib. These results suggest BBR only affects specific DNA repair pathways. Western blot showed BBR down-regulated XRCC1 expressions, and the rescued XRCC1 recovered the resistance of cancer cells to BBR. Therefore, we conclude that BBR interferes with XRCC1-mediated base excision repair to sensitize cancer cells to chemotherapeutic drugs. These finding can contribute to understanding the effects of BBR on cellular DNA repair and the clinical employment of BBR in treatment of breast cancer.

Keywords: Berberine; DNA damage agents; XRCC1; base excision repair; breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Berberine / pharmacology*
  • Breast Neoplasms / pathology*
  • Camptothecin / pharmacology
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cisplatin / pharmacology
  • DNA Breaks / drug effects
  • DNA Repair / drug effects*
  • Down-Regulation / drug effects
  • Female
  • Humans
  • Hydroxyurea / pharmacology
  • Neoplasm Proteins / metabolism
  • Phthalazines / pharmacology
  • Piperazines / pharmacology
  • S Phase / drug effects
  • X-ray Repair Cross Complementing Protein 1 / metabolism*

Substances

  • Antineoplastic Agents
  • Neoplasm Proteins
  • Phthalazines
  • Piperazines
  • X-ray Repair Cross Complementing Protein 1
  • XRCC1 protein, human
  • Berberine
  • Cisplatin
  • olaparib
  • Hydroxyurea
  • Camptothecin