Differential responses of proliferative and non-proliferative leukemia cells to oxidative stress.
The response of three human leukemia cell lines, the proliferative promonocyte THP-1 and the promyeloid HL60 cells and the non-proliferative phorbol ester-treated HL60 cells (HL60/PMA), to oxidative stress induced by tert-butylhydroperoxide (t-BHP) treatment was analyzed by fluorescence microplate assay, anti-oxidant enzyme activity measurements, high performance liquid chromatography, yopro-1/PI incorporation, poly (ADP-ribose) polymerase and caspase 3 cleavages. After t-BHP treatment, the non-proliferative HL60/PMA cells exhibited a weak increase in reactive oxygen species (ROS) production, a better preservation of thiol content, a decrease of glutathione peroxidase activity and a high ability to undergo necrosis rather than apoptosis. Submitted to the same treatment, the proliferative HL60 and THP-1 cells exhibited a high increase of ROS production, a moderate thiol depletion and a high percentage of apoptosis. Under thiol depleting conditions, the oxidative treatment of the HL60/PMA cells resulted in a high ROS production that reached levels similar to those of the two other cell lines and in cell death mainly by necrosis. In conclusion, these results that show proliferative phenotype is essential for cell response towards oxidative stress, are of particular interest in chemotherapy involving an oxidative mechanism.
Plantin-Carrenard
Emmanuelle
E
Laboratoire de Biochimie Générale et de Glycobiologie, U.F.R. des Sciences Pharmaceutiques et Biologiques, Université René Descartes Paris 5, 4 avenue de l'Observatoire 75006 Paris, France.
Bernard
Maguy
M
Derappe
Christian
C
Bringuier
Annie
A
Vadrot
Nathalie
N
Feldmann
Gerard
G
Foglietti
Marie-José
MJ
Aubery
Michèle
M
Braut-Boucher
Françoise
F
D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D016923:Cell Death; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002851:Chromatography, High Pressure Liquid; D003545:Cysteine / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000737:chemistry / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D007938:Leukemia / Q000378:metabolism / Q000473:pathology*; D009336:Necrosis; D018384:Oxidative Stress; D010100:Oxygen / Q000737:chemistry; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D017382:Reactive Oxygen Species; D013050:Spectrometry, Fluorescence; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors
D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D005978:Glutathione; D003545:Cysteine; D013755:Tetradecanoylphorbol Acetate; D010100:Oxygen