Inhibition of repair-related DNA polymerases by vitamin Ks, their related quinone derivatives and associated inflammatory activity (Review)

  • Authors:
    • Yoshiyuki Mizushina
    • Shin Nishiumi
    • Masayuki Nishida
    • Hiromi Yoshida
    • Takeshi Azuma
    • Masaru Yoshida
  • View Affiliations

  • Published online on: January 15, 2013     https://doi.org/10.3892/ijo.2013.1771
  • Pages: 793-802
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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.
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March 2013
Volume 42 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Mizushina Y, Nishiumi S, Nishida M, Yoshida H, Azuma T and Yoshida M: Inhibition of repair-related DNA polymerases by vitamin Ks, their related quinone derivatives and associated inflammatory activity (Review). Int J Oncol 42: 793-802, 2013.
APA
Mizushina, Y., Nishiumi, S., Nishida, M., Yoshida, H., Azuma, T., & Yoshida, M. (2013). Inhibition of repair-related DNA polymerases by vitamin Ks, their related quinone derivatives and associated inflammatory activity (Review). International Journal of Oncology, 42, 793-802. https://doi.org/10.3892/ijo.2013.1771
MLA
Mizushina, Y., Nishiumi, S., Nishida, M., Yoshida, H., Azuma, T., Yoshida, M."Inhibition of repair-related DNA polymerases by vitamin Ks, their related quinone derivatives and associated inflammatory activity (Review)". International Journal of Oncology 42.3 (2013): 793-802.
Chicago
Mizushina, Y., Nishiumi, S., Nishida, M., Yoshida, H., Azuma, T., Yoshida, M."Inhibition of repair-related DNA polymerases by vitamin Ks, their related quinone derivatives and associated inflammatory activity (Review)". International Journal of Oncology 42, no. 3 (2013): 793-802. https://doi.org/10.3892/ijo.2013.1771