Induction of apoptosis in K562 human leukemia cells by 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone

Leuk Res. 2005 Aug;29(8):887-92. doi: 10.1016/j.leukres.2005.01.006. Epub 2005 Feb 16.

Abstract

2',4'-Dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC), isolated from the buds of Cleistocalyx operculatus, was investigated in its cytotoxicity and anti-proliferation on K562 cell line. Our results revealed that the IC50 was equal to 14.2+/-0.45 microM and the EC50 was 3.3+/-0.14 microM. Staining with Hoechst 33258 showed fragmentation and condensation of chromatin in the cells treated with 8 microM DMC for 48 h. Flow cytometric analysis was performed to determine hypodiploid cells. The results of flow cytometry assay indicated that the percentage of hypodiploid K562 cells was 76.15+/-3.22% after 48 h treatment with 16.0 microM DMC. The treatment resulted in the appearance of a hypodiploid peak (A0 region), probably due to the presence of apoptosing cells and/or apoptotic bodies with DNA content less than 2n. Western blot results illustrated that in the same dosage and incubation time, DMC could down-regulate the level of Bcl-2 protein and did not influence the expression of Bax protein. The resulting net effect could thus lead to a lower ratio of Bcl-2/Bax, which might be responsible for the DMC-induced apoptosis in K562 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Cell Nucleus / drug effects
  • Cell Survival / drug effects
  • Chalcone / analogs & derivatives*
  • Chalcone / pharmacology*
  • Chalcones
  • Colony-Forming Units Assay
  • Diploidy
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • K562 Cells
  • Leukemia, Erythroblastic, Acute / drug therapy*
  • Leukemia, Erythroblastic, Acute / pathology
  • Molecular Structure
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • Proto-Oncogene Proteins c-bcl-2 / drug effects
  • bcl-2-Associated X Protein

Substances

  • 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone
  • BAX protein, human
  • Chalcones
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • Chalcone