Synergistic anti-cancer activity of the combination of dihydroartemisinin and doxorubicin in breast cancer cells

Pharmacol Rep. 2013;65(2):453-9. doi: 10.1016/s1734-1140(13)71021-1.

Abstract

Background: Dihydroartemisinin (DHA) exhibits potent anti-malarial and anti-cancer activities. This study aimed to investigate the anti-proliferative effects of a combination of DHA and doxorubicin (DOX) on human breast cancer cells.

Methods: MTT assay and the combination index (CI) were used to show the anti-proliferative effects and calculate the synergism potential, respectively. Flow cytometry assay was used to detect apoptosis and the intracellular accumulation of DOX. JC-1 staining was used to determine the mitochondrial membrane potential. Western blot analysis was used to detect the protein expression of some apoptosis-related molecules.

Results: Asynergistic anti-proliferative effect was found, and the enhanced anti-cancer activity was observed to be accompanied by the prompt onset of apoptosis in MCF-7 cells. The combinative treatment remarkably decreased the mitochondrial membrane potential and activated caspase cascades more than the mono-treatment. Pretreatment with DHA also did not influence the accumulation of DOX in MCF-7 cells.

Conclusion: This study presented a new opportunity to enhance the effectiveness of future treatment regimens of breast cancer using DOX.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects*
  • Artemisinins / administration & dosage
  • Artemisinins / pharmacology*
  • Blotting, Western
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Caspases / metabolism
  • Cell Proliferation / drug effects
  • Doxorubicin / administration & dosage
  • Doxorubicin / pharmacology*
  • Drug Synergism
  • Female
  • Flow Cytometry
  • Humans
  • MCF-7 Cells
  • Membrane Potential, Mitochondrial / drug effects

Substances

  • Antineoplastic Agents
  • Artemisinins
  • artenimol
  • Doxorubicin
  • Caspases