Pure total flavonoids from Citrus paradisi Macfadyen act synergistically with arsenic trioxide in inducing apoptosis of Kasumi-1 leukemia cells in vitro

J Zhejiang Univ Sci B. 2015 Jul;16(7):580-5. doi: 10.1631/jzus.B1400234.


To investigate the potential effects of pure total flavonoid compounds (PTFCs) from Citrus paradisi Macfadyen separately or combined with arsenic trioxide on the proliferation of human myeloid leukemia cells and the mechanisms underlying the action of PTFCs. The effects of PTFCs separately or combined with arsenic trioxide on the proliferation and apoptosis of leukemia cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), fluorescence microscopy, and flow cytometry. Their effects on the expression levels of apoptosis-related regulators were determined by Western blot assay. PTFCs combined with arsenic trioxide significantly inhibited the growth of Kasumi-1 cells, and apoptosis was confirmed by flow cytometry analysis. Hoechst 33258 staining showed more significant morphological changes and more apoptosis following the combined treatment. Western blots showed changes in the expression of genes for poly ADP-ribose polymerase (PARP), caspase 3/9, and P65. The results indicated that PTFCs separately or combined with arsenic trioxide inhibited proliferation of leukemia cells in vitro and induced their apoptosis by modulating the expression of apoptosis-related regulator genes.

Keywords: Apoptosis; Growth inhibition; Human myeloid leukemia cells; Pure total flavonoid compounds; Synergistic effect.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Apoptosis / drug effects*
  • Arsenic Trioxide
  • Arsenicals / administration & dosage*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Synergism
  • Flavonoids / administration & dosage*
  • Humans
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / pathology
  • Oxides / administration & dosage*
  • Plant Extracts / administration & dosage*
  • Treatment Outcome


  • Antineoplastic Agents
  • Arsenicals
  • Flavonoids
  • Oxides
  • Plant Extracts
  • Arsenic Trioxide