Inhibitory effects of vitamin K3 derivatives on DNA polymerase and inflammatory activity

  • Authors:
    • Aoganghua Aoganghua
    • Shin Nishiumi
    • Kazuki Kobayashi
    • Masayuki Nishida
    • Kouji Kuramochi
    • Kazunori Tsubaki
    • Midori Hirai
    • Shinwa Tanaka
    • Takeshi Azuma
    • Hiromi Yoshida
    • Yoshiyuki Mizushina
    • Masaru Yoshida
  • View Affiliations

  • Published online on: August 11, 2011     https://doi.org/10.3892/ijmm.2011.773
  • Pages: 937-945
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Abstract

Previously, we reported that vitamin K3 (menadione, 2-methyl-1,4-naphthoquinone) (compound 2) inhibits the activity of human mitochondrial DNA polymerase γ (pol γ). In this study, we investigated the inhibitory effects (IEs) of vitamin K3 and its derivatives, such as 1,4-naphthoquinone (compound 1) and 1,2-dimethyl-1,4-naphthoquinone (compound 3), on the activity of mammalian pols. Among compounds 1-3 (10 µM for each), compound 1 was the strongest inhibitor of mammalian pols α and λ, which belong to the B and X pol families, respectively, whereas compound 2 was the strongest inhibitor of human pol γ, a family A pol. However, these compounds did not affect the activity of human pol κ, a family Y pol. As we previously found a positive relationship between pol λ inhibition and anti-inflammatory action, we examined whether these vitamin K3 derivatives are able to inhibit inflammatory responses. Among the three compounds tested, compound 1 caused the greatest reduction in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced acute inflammation in mouse ears. In addition, in a cell culture system using RAW264.7 mouse macrophages, compound 1 displayed the strongest suppression of tumor necrosis factor (TNF)-α production induced by lipopolysaccharide (LPS). In an in vivo mouse model of LPS-evoked acute inflammation, the intraperitoneal injection of compound 1 into mice suppressed TNF-α production in their peritoneal macrophages and serum. In an in vivo colitis mouse model induced using dextran sulfate sodium (DSS), the vitamin K3 derivatives markedly suppressed DSS-evoked colitis. In conclusion, this study has identified several vitamin K3 derivatives, such as compound 1, that are promising anti-inflammatory candidates.

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December 2011
Volume 28 Issue 6

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Aoganghua A, Nishiumi S, Kobayashi K, Nishida M, Kuramochi K, Tsubaki K, Hirai M, Tanaka S, Azuma T, Yoshida H, Yoshida H, et al: Inhibitory effects of vitamin K3 derivatives on DNA polymerase and inflammatory activity. Int J Mol Med 28: 937-945, 2011.
APA
Aoganghua, A., Nishiumi, S., Kobayashi, K., Nishida, M., Kuramochi, K., Tsubaki, K. ... Yoshida, M. (2011). Inhibitory effects of vitamin K3 derivatives on DNA polymerase and inflammatory activity. International Journal of Molecular Medicine, 28, 937-945. https://doi.org/10.3892/ijmm.2011.773
MLA
Aoganghua, A., Nishiumi, S., Kobayashi, K., Nishida, M., Kuramochi, K., Tsubaki, K., Hirai, M., Tanaka, S., Azuma, T., Yoshida, H., Mizushina, Y., Yoshida, M."Inhibitory effects of vitamin K3 derivatives on DNA polymerase and inflammatory activity". International Journal of Molecular Medicine 28.6 (2011): 937-945.
Chicago
Aoganghua, A., Nishiumi, S., Kobayashi, K., Nishida, M., Kuramochi, K., Tsubaki, K., Hirai, M., Tanaka, S., Azuma, T., Yoshida, H., Mizushina, Y., Yoshida, M."Inhibitory effects of vitamin K3 derivatives on DNA polymerase and inflammatory activity". International Journal of Molecular Medicine 28, no. 6 (2011): 937-945. https://doi.org/10.3892/ijmm.2011.773