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

Journal of Cellular Biochemistry
Seong-Su HanSeyeon Park

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 microM 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 sug...Continue Reading

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Citations

Sep 5, 2006·Apoptosis : an International Journal on Programmed Cell Death·Prachee GokhaléMargret C M Vissers
Apr 30, 2013·Antioxidants & Redox Signaling·Nermi L ParrowMark Levine
Sep 15, 2005·Proceedings of the National Academy of Sciences of the United States of America·Qi ChenMark Levine
Apr 15, 2017·Journal of Cellular Biochemistry·Jong-Eun KimKi Won Lee
Jul 11, 2008·Journal of Cellular Biochemistry·Seyeon ParkYong-Woo Hong
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Jul 14, 2021·Antioxidants & Redox Signaling·Christophe Glorieux, Pedro Buc Calderon

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