Inhibitory effects of sulfobacin B on DNA polymerase and inflammation

  • Authors:
    • Jun Maeda
    • Masayuki Nishida
    • Hirosato Takikawa
    • Hiromi Yoshida
    • Takeshi Azuma
    • Masaru Yoshida
    • Yoshiyuki Mizushina
  • View Affiliations

  • Published online on: November 1, 2010     https://doi.org/10.3892/ijmm_00000522
  • Pages: 751-758
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Abstract

The sulfonolipid, sulfobacin B, is isolated from Chryseobacterium sp. and functions both as a von Willebrand factor receptor antagonist and a DNA polymerase (pol) α inhibitor. Previously, we chemically synthesized sulfobacin B by starting from L-cysteine. In this study, we investigated the inhibitory effects of chemically synthesized sulfobacin B on the activity of pols and other DNA metabolic enzymes. Sulfobacin B selectively inhibited the activity of all animal pol species: Among the pols tested, the inhibitory effect of the compound on pol λ activity was the strongest with IC50 values of 1.6 µM. However, sulfobacin B did not influence the activity of plant or prokaryotic pols, or that of the other DNA metabolic enzymes such as primase of pol α, RNA polymerase, polynucleotide kinase or deoxyribonuclease I. As we previously found a positive relationship between pol λ inhibition and anti-inflammation, we examined whether sulfobacin B could inhibit inflammatory responses. The compound caused a marked reduction in 12-O-tetradecanoylphorbol-13-acetate-induced acute inflammation in the mouse ear. In a cell culture system using mouse macrophages, sulfobacin B strongly inhibited the production of tumor necrosis factor (TNF)-α and the action of nuclear factor-κB induced by lipopolysaccharide (LPS). In an in vivo mouse model of LPS-induced acute inflammation, the intraperitoneal injection of sulfobacin B to mice led to the suppression of serum TNF-α production. These results indicate that sulfobacin B is a potential chemotherapeutic agent for inflammation.

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November 2010
Volume 26 Issue 5

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

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Spandidos Publications style
Maeda J, Nishida M, Takikawa H, Yoshida H, Azuma T, Yoshida M and Mizushina Y: Inhibitory effects of sulfobacin B on DNA polymerase and inflammation . Int J Mol Med 26: 751-758, 2010.
APA
Maeda, J., Nishida, M., Takikawa, H., Yoshida, H., Azuma, T., Yoshida, M., & Mizushina, Y. (2010). Inhibitory effects of sulfobacin B on DNA polymerase and inflammation . International Journal of Molecular Medicine, 26, 751-758. https://doi.org/10.3892/ijmm_00000522
MLA
Maeda, J., Nishida, M., Takikawa, H., Yoshida, H., Azuma, T., Yoshida, M., Mizushina, Y."Inhibitory effects of sulfobacin B on DNA polymerase and inflammation ". International Journal of Molecular Medicine 26.5 (2010): 751-758.
Chicago
Maeda, J., Nishida, M., Takikawa, H., Yoshida, H., Azuma, T., Yoshida, M., Mizushina, Y."Inhibitory effects of sulfobacin B on DNA polymerase and inflammation ". International Journal of Molecular Medicine 26, no. 5 (2010): 751-758. https://doi.org/10.3892/ijmm_00000522