Curcumin activates DNA repair pathway in bone marrow to improve carboplatin-induced myelosuppression

Sci Rep. 2017 Dec 18;7(1):17724. doi: 10.1038/s41598-017-16436-9.

Abstract

Carboplatin, a second-generation platinum agent, has been used as a cancer therapy for decades and exhibits strong anti-tumor activity. However, the wide application of carboplatin is largely limited due to its side effects, especially myelosuppression. Here, we combined carboplatin with curcumin, a natural product that improves tumor-induced anemia, for the treatment of fibrosarcoma to improve the side effects of carboplatin. We first examined the synergistic and attenuated effects of the two agents in a T241-bearing mouse model. The combination therapy caused no obvious synergistic effect, but curcumin significantly improved the survival rate of carboplatin-treated mice. Histologic analysis of the kidney and bone marrow revealed that curcumin improved carboplatin-induced myelosuppression but did not affect the kidney. To determine the mechanism involved, we introduced a probe derived from curcumin to identify its targets in bone marrow cells and the results provided us a clue that curcumin might affect the DNA repair pathway. Western blot analysis revealed that curcumin up-regulated BRCA1, BRCA2 and ERCC1 expression in bone marrow. In conclusion, curcumin attenuates carboplatin-induced myelosuppression by activating the DNA repair pathway in bone marrow cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Apoptosis / drug effects
  • Bone Marrow / drug effects
  • Bone Marrow / metabolism
  • Bone Marrow Cells / metabolism
  • Carboplatin / pharmacology
  • Cell Culture Techniques
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • China
  • Curcumin / pharmacology*
  • DNA Repair / drug effects*
  • DNA-Binding Proteins / drug effects
  • Disease Models, Animal
  • Drug Synergism
  • Endonucleases / drug effects
  • Fibrosarcoma / drug therapy*
  • Genes, BRCA1 / drug effects
  • Genes, BRCA2 / drug effects
  • Granulocyte Precursor Cells / drug effects
  • Mice
  • Mice, Inbred C57BL

Substances

  • DNA-Binding Proteins
  • Carboplatin
  • ERCC1 protein, human
  • Endonucleases
  • Curcumin