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NADPH oxidase is involved in protein kinase CKII down‐regulation‐mediated senescence through elevation of the level of reactive oxygen species in human colon cancer cells
Author(s) -
Jeon Seon Min,
Lee Sung-Jin,
Kwon Taeg Kyu,
Kim Kyung-Jin,
Bae Young-Seuk
Publication year - 2010
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/j.febslet.2010.05.054
Subject(s) - superoxide , apocynin , nadph oxidase , chemistry , small interfering rna , reactive oxygen species , intracellular , kinase , casein kinase 2 , protein kinase a , microbiology and biotechnology , biochemistry , biology , transfection , enzyme , cyclin dependent kinase 2 , gene
We have shown that protein kinase CKII (CKII) inhibition induces senescence through the p53‐dependent pathway in HCT116 cells. Here we examined the molecular mechanism through which CKII inhibition activates p53 in HCT116 cells. CKII inhibition by treatment with CKII inhibitor or CKIIα small‐interfering RNA (siRNA) increased intracellular hydrogen peroxide and superoxide anion levels. These effects were significantly blocked by pretreatment of cells with the antioxidant N ‐acetylcysteine. Additionally, NADPH oxidase (NOX) inhibitor apocynin and p22 phox siRNA significantly reduced p53 expression and suppressed the appearance of senescence markers. CKII inhibition did not affect mitochondrial superoxide generation. These data demonstrate that CKII inhibition induces superoxide anion generation via NOX activation, and subsequent superoxide‐dependent activation of p53 acts as a mediator of senescence in HCT116 cells after down‐regulation of CKII.