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L ‐ascorbic acid represses constitutive activation of NF‐κB and COX‐2 expression in human acute myeloid leukemia, HL‐60
Author(s) -
Han SeongSu,
Kim Kihyun,
Hahm EunRyeong,
Lee Sook J.,
Surh YoungJoon,
Park Hye K.,
Kim Won S.,
Jung Chul W.,
Lee Mark H.,
Park Keunchil,
Yang JungHyun,
Yoon SungSoo,
Riordan Neil H.,
Riordan Hugh D.,
Kimler Bruce F.,
Park Chan H.,
Lee JeHo,
Park Seyeon
Publication year - 2004
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.20116
Subject(s) - p50 , nf κb , chemistry , downregulation and upregulation , ascorbic acid , relb , transcription factor , iκbα , psychological repression , inhibitory postsynaptic potential , arsenic trioxide , microbiology and biotechnology , biochemistry , cancer research , apoptosis , gene expression , biology , gene , endocrinology , food science
There is increasing evidence that l ‐ascorbic acid (LAA) is selectively toxic to some types of cancer cells at pharmacological concentrations, functioning as a pro‐oxidant rather than as an anti‐oxidant. However, the molecular mechanisms by which LAA initiates cellular signaling leading to cell death are still unclear. In an effort to gain insight into these mechanisms, the effects of LAA on eukaryotic transcription nuclear factor NF‐κB and cyclooxygenase‐2 (COX‐2) expression were investigated. In the present study, LAA suppressed DNA binding activity of NF‐κB, composed of a p65/p50 heterodimer, through inhibition of degradation of inhibitory κB‐α (IκB‐α) and prevention of nuclear translocation of p65. The inhibitory effect of LAA on NF‐κB activity was dependent upon glutathione levels in HL‐60 cells, as well as generation of H 2 O 2 but not superoxide anion. LAA also downregulated the expression of COX‐2, which has a NF‐κB binding site on its promoter, through repressing NF‐κB DNA binding activity. Moreover, cotreatment of 1 μM arsenic trioxide (As 2 O 3 ) with various concentrations of LAA enhanced an LAA‐induced repression of NF‐κB activity and COX‐2 expression. In conclusion, our data suggest that LAA exerts its anti‐tumor activity through downregulation of NF‐κB activity and COX‐2 expression, and these inhibitory effects can be enhanced by co‐treatment with As 2 O 3 . © 2004 Wiley‐Liss, Inc.