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L-ascorbic acid represses constitutive activation of NF-κB and COX-2 expression in human acute myeloid leukemia, HL-60 : L-ascorbic acid represses constitutive activation of NF-kappa B and COX-2 expression in human acute myeloid leukemia, HL-60

Cited 36 time in Web of Science Cited 37 time in Scopus
Authors

Han, Seong‐Su; Kim, Kihyun; Hahm, Eun‐Ryeong; Lee, Sook J.; Surh, Young‐Joon; Park, Hye K.; Kim, Won S.; Jung, Chul W.; Lee, Mark H.; Park, Keunchil; Yang, Jung‐Hyun; Yoon, Sung‐Soo; Riordan, Neil H.; Riordan, Hugh D.; Kimler, Bruce F.; Park, Chan H.; Lee, Je‐Ho; Park, Seyeon

Issue Date
2004-10
Publisher
John Wiley & Sons Inc.
Citation
Journal of Cellular Biochemistry, Vol.93 No.2, pp.257-270
Abstract
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-kappaB and cyclooxygenase-2 (COX-2) expression were investigated. In the present study, LAA suppressed DNA binding activity of NF-kappaB, composed of a p65/p50 heterodimer, through inhibition of degradation of inhibitory kappaB-alpha (IkappaB-alpha) and prevention of nuclear translocation of p65. The inhibitory effect of LAA on NF-kappaB activity was dependent upon glutathione levels in HL-60 cells, as well as generation of H2O2 but not superoxide anion. LAA also downregulated the expression of COX-2, which has a NF-kappaB binding site on its promoter, through repressing NF-kappaB DNA binding activity. Moreover, cotreatment of 1 muM arsenic trioxide (As2O3) with various concentrations of LAA enhanced an LAA-induced repression of NF-kappaB activity and COX-2 expression. In conclusion, our data suggest that LAA exerts its anti-tumor activity through downregulation of NF-kappaB activity and COX-2 expression, and these inhibitory effects can be enhanced by co-treatment with As2O3. (C) 2004 Wiley-Liss, Inc.
ISSN
0730-2312
URI
https://hdl.handle.net/10371/172781
DOI
https://doi.org/10.1002/jcb.20116
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College of Pharmacy (약학대학)Dept. of Pharmacy (약학과)Journal Papers (저널논문_약학과)
College of Medicine/School of Medicine (의과대학/대학원)Dept. of Medicine (의학과)Journal Papers (저널논문_의학과)
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