Superoxide anion inhibits drug-induced tumor cell death.
Intracellular superoxide (O(2)*- was manipulated in M14 melanoma cells by overexpression or repression of Cu/Zn SOD using a tetracycline-inducible expression system. Scavenging intracellular O(2)*- increased tumor cell sensitivity to daunorubicin, etoposide, and pMC540, whereas expression of the antisense SOD mRNA significantly decreased cell sensitivity to drug treatment. Whereas Cu/Zn SOD overexpressing cells exhibited higher activation of the executioner caspase 3 upon drug exposure, caspase 3 activation was significantly lower when Cu/Zn SOD was repressed by antisense expression. These data show that intracellular O(2)*- regulates tumor cell response to drug-induced cell death via a direct or indirect effect on the caspase activation pathway.
Pervaiz
S
S
Department of Physiology, National University of Singapore, Singapore.
Ramalingam
J K
JK
Hirpara
J L
JL
Clément
M V
MV
D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D003630:Daunorubicin / Q000494:pharmacology; D004347:Drug Interactions; D004789:Enzyme Activation; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology; D011744:Pyrimidinones / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000235:genetics; D013481:Superoxides / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000378:metabolism
D020319:Oligodeoxyribonucleotides, Antisense; D011744:Pyrimidinones; D012333:RNA, Messenger; D019014:fas Receptor; D013481:Superoxides; C003954:merocyanine dye; D005047:Etoposide; D013482:Superoxide Dismutase; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D003630:Daunorubicin