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Superoxide anion inhibits drug‐induced tumor cell death
Author(s) -
Pervaiz Shazib,
Ramalingam Jeya Kumar,
Hirpara Jayshreekumari L,
Clément Marie-Véronique
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)01258-2
Subject(s) - superoxide , programmed cell death , chemistry , drug , microbiology and biotechnology , cancer research , pharmacology , biophysics , biochemistry , apoptosis , biology , enzyme
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.