ART-induced biophysical and biochemical alterations of Jurkat cell membrane.
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.
Cai
Xiaofang
X
Department of Chemistry, Jinan University, Guangzhou, Guangdong 510632, China. xiaofang3309@163.com
You
Pengtao
P
Cai
Jiye
J
Yang
Xiaoxi
X
Chen
Qian
Q
Huang
Feicheng
F
D000199:Actins / Q000378:metabolism; D000962:Antimalarials / Q000378:metabolism*; D037621:Artemisinins / Q000378:metabolism*; D000077332:Artesunate; D015153:Blotting, Western; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism; D053148:Caspase 3 / Q000032:analysis; D002462:Cell Membrane / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D048429:Cell Size; D019938:Cyclin D1 / Q000032:analysis; D003593:Cytoplasm / Q000737:chemistry; D015536:Down-Regulation; D004548:Elasticity; D006801:Humans; D019169:Jurkat Cells; D018625:Microscopy, Atomic Force; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D000199:Actins; D000962:Antimalarials; D037621:Artemisinins; D019938:Cyclin D1; D000077332:Artesunate; D053148:Caspase 3; D017301:Ca(2+) Mg(2+)-ATPase; D000254:Sodium-Potassium-Exchanging ATPase