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Inhibition of repair-related DNA polymerases by vitamin Ks, their related quinone derivatives and associated inflammatory activity (Review).
- Source :
-
International journal of oncology [Int J Oncol] 2013 Mar; Vol. 42 (3), pp. 793-802. Date of Electronic Publication: 2013 Jan 15. - Publication Year :
- 2013
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Abstract
- Vitamin Ks (VKs) are fat-soluble quinone compounds known to have various bioactivities. This review describes the inflammatory effects of VKs and their related quinone derivatives based on DNA polymerase (pol) inhibition. VK3, but not VK1 or VK2 (=MK-4), inhibited the activity of human pol γ, which is the DNA replicative pol in mitochondria. Of the intermediate compounds between VK2 and VK3 (namely MK-3, MK-2 and MK-1), MK-2 was the strongest inhibitor of mammalian pols α, κ and λ, which belong to the B-, Y- and X-families of pols, respectively. Among the VK3 based quinone derivatives, such as 1,4-naphthoquinone (NQ), 2-dimethyl-1,4-naphthoquinone (1,2-dimethyl-NQ), 1,4-benzoquinone (BQ), 9,10-anthraquinone (AQ) and 5,12-naphthacenequinone (NCQ), NQ was the strongest inhibitor of mammalian pols α and λ, in particular, DNA repair-related pol λ. Among the all compounds tested, NQ displayed the strongest suppression of tumor necrosis factor (TNF)-α production induced by lipopolysaccharide (LPS) in a cell culture system using RAW264.7 mouse macrophages. NQ also suppressed the expression of pol λ protein in these cells, after LPS-treated RAW264.7 cells were stimulated to induce pol λ expression. In an in vivo mouse model of LPS-evoked acute inflammation, intraperitoneal injection of NQ into mice suppressed TNF-α production in peritoneal macrophages and serum. In an in vivo colitis mouse model induced using dextran sulfate sodium (DSS), NQ markedly suppressed DSS-evoked colitis. The promising anti-inflammatory candidates based on the inhibition of DNA repair-related pols, such as pol λ, by VKs quinone derivatives, such as NQ, are discussed.
- Subjects :
- Animals
DNA Polymerase I antagonists & inhibitors
DNA Polymerase beta antagonists & inhibitors
DNA Polymerase gamma
DNA Repair
DNA-Directed DNA Polymerase
Humans
Inflammation
Mice
Mitochondria genetics
Mitochondria metabolism
Tumor Necrosis Factor-alpha antagonists & inhibitors
Naphthoquinones pharmacology
Nucleic Acid Synthesis Inhibitors
Tumor Necrosis Factor-alpha biosynthesis
Vitamin K analogs & derivatives
Vitamin K chemistry
Vitamin K metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1791-2423
- Volume :
- 42
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- International journal of oncology
- Publication Type :
- Academic Journal
- Accession number :
- 23338798
- Full Text :
- https://doi.org/10.3892/ijo.2013.1771