Artesunate Induces SKM-1 Cells Apoptosis by Inhibiting Hyperactive β-catenin Signaling Pathway

Int J Med Sci. 2015 Jun 11;12(6):524-9. doi: 10.7150/ijms.11352. eCollection 2015.

Abstract

Introduction: Artesunate (ART), a wildly used agent to treat severe malarial around the world, also has the power to inhibit growth of different types of tumor. However, the exact molecular mechanisms keep unknown.

Method: In this study, we used myelodysplastic syndrome (MDS) cells (SKM-1 cells) with differential ART concentrations treatment at multiple time points to observe the subsequence cell function alteration and the possible involved pathway genes.

Results: We found that ART demonstrated the ability to inhibit proliferation and induce apoptosis in SKM-1 in a dose and time-dependent manner. Demethylase recovered CDH1 gene expression may be involved in the apoptosis process. The β-catenin protein translocated from the nucleus and cytoplasm to the membrane result in inactivation of β-catenin signaling pathway.

Conclusion: Our findings provide a rational basis to develop ART as a useful therapeutic agent for the treatment of myelodysplastic syndromes.

Keywords: Artesunate (ART); E-cadherin; myelodysplastic syndrome; β-catenin pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD
  • Antineoplastic Agents / administration & dosage
  • Apoptosis / drug effects
  • Artemisinins / administration & dosage*
  • Artesunate
  • Cadherins / biosynthesis*
  • Cadherins / genetics
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / pathology
  • Signal Transduction / drug effects
  • beta Catenin / biosynthesis
  • beta Catenin / genetics*

Substances

  • Antigens, CD
  • Antineoplastic Agents
  • Artemisinins
  • CDH1 protein, human
  • Cadherins
  • beta Catenin
  • Artesunate