Mechanism of cell death induced by an antioxidant extract of Cratoxylum cochinchinense (YCT) in Jurkat T cells: the role of reactive oxygen species and calcium.
YCT is a semipurified extract from Cratoxylum cochinchinense that has antioxidant properties and contains mostly mangiferin. We show here that YCT is selectively toxic to certain cell types and investigate the mechanisms of this toxicity in Jurkat T cells. By flow cytometric analyses, we show that YCT causes intense oxidative stress and a rise in cytosolic Ca(2+). This is followed by a rise in mitochondrial Ca(2+), release of cytochrome c, collapse of Deltapsi(m), a fall in ATP levels, and eventually cell death. The mechanism(s) of intense oxidative stress may involve a plasma membrane redox system, as cell death is inhibited by potassium ferricyanide. Cell death has some features of apoptosis (propidium iodide staining, externalization of phosphatidylserine, limited caspase-3 and -9 activities), but there was no internucleosomal DNA fragmentation.
Tang
Soon Yew
SY
Department of Biochemistry, Faculty of Medicine, National University of Singapore, Singapore.
Whiteman
Matthew
M
Jenner
Andrew
A
Peng
Zhao Feng
ZF
Halliwell
Barry
B
D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D002448:Cell Adhesion; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002470:Cell Survival; D028084:Clusiaceae / Q000378:metabolism*; D004396:Coloring Agents / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation; D004285:Dogs; D005292:Ferricyanides / Q000494:pharmacology; D005434:Flow Cytometry; D005978:Glutathione / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D019169:Jurkat Cells; D008214:Lymphocytes / Q000378:metabolism; D008564:Membrane Potentials; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D009707:Nucleosomes / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D016716:PC12 Cells; D010718:Phosphatidylserines / Q000737:chemistry; D010936:Plant Extracts / Q000494:pharmacology; D051381:Rats; D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors; D014343:Trypan Blue / Q000494:pharmacology
D000975:Antioxidants; D004396:Coloring Agents; D005292:Ferricyanides; D009707:Nucleosomes; D010718:Phosphatidylserines; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts; D013844:Thiazoles; D000255:Adenosine Triphosphate; D045304:Cytochromes c; C505407:CASP3 protein, human; C506433:CASP9 protein, human; C505410:Casp3 protein, rat; C506435:Casp9 protein, rat; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases; C022616:thiazolyl blue; D005978:Glutathione; D014343:Trypan Blue; D002118:Calcium; C028033:potassium ferricyanide