ART-induced biophysical and biochemical alterations of Jurkat cell membrane

Micron. 2011 Jan;42(1):17-28. doi: 10.1016/j.micron.2010.08.009. Epub 2010 Sep 8.

Abstract

Integrity of the cell membrane is a basic requirement for maintaining the biological characteristics of a cell. In this study, cell membrane as the target of drug action was investigated. CCK-8 assay suggested that Artesunate (ART) could significantly suppress the proliferation of Jurkat cells in a dose-dependent manner. Changes in the morphology and mechanics of Jurkat cells were studied by atomic force microscopy (AFM). These changes included decrease of Young's modulus (from 3.18±0.54 to 1.72±0.54kPa), increase in the fluctuation of surface components, increase in shrinkage, or even the appearance of pores. The Young's modulus change was according to the F-actin protein, not the Tubulin-β or integrin β1 protein. Meanwhile, the activities of plasma membrane Ca(2+)-Mg(2+)-ATPase and Na(+)-K(+)-ATPase were also repressed following ART exposure as well as membrane potential. Western blot was used to detect Caspase 3 and Cyclin D1 protein level. The Cyclin D1 was downregulated and Caspase 3 was activated. Hence, cellular membrane represented a plausible target for ART-induced injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Antimalarials / metabolism*
  • Artemisinins / metabolism*
  • Artesunate
  • Blotting, Western
  • Ca(2+) Mg(2+)-ATPase / metabolism
  • Caspase 3 / analysis
  • Cell Membrane / drug effects*
  • Cell Membrane / physiology
  • Cell Membrane / ultrastructure
  • Cell Size
  • Cyclin D1 / analysis
  • Cytoplasm / chemistry
  • Down-Regulation
  • Elasticity
  • Humans
  • Jurkat Cells
  • Microscopy, Atomic Force
  • Sodium-Potassium-Exchanging ATPase / metabolism

Substances

  • Actins
  • Antimalarials
  • Artemisinins
  • Cyclin D1
  • Artesunate
  • Caspase 3
  • Ca(2+) Mg(2+)-ATPase
  • Sodium-Potassium-Exchanging ATPase