Selective Inhibition of Mammalian DNA Polymerase α by Vitamin D2 and D3

  • Mizushina Yoshiyuki
    Laboratory of Food & Nutritional Sciences, Department of Nutritional Science, Kobe-Gakuin University High Technology Research Center, Kobe-Gakuin University
  • Xu Xianai
    Laboratory of Food & Nutritional Sciences, Department of Nutritional Science, Kobe-Gakuin University
  • Okano Toshio
    Department of Hygienic Sciences, Kobe Pharmaceutical University
  • Murakami Chikako
    Laboratory of Food & Nutritional Sciences, Department of Nutritional Science, Kobe-Gakuin University
  • Takemura Masaharu
    Laboratory of Cancer Cell Biology, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine
  • Yoshida Hiromi
    Laboratory of Food & Nutritional Sciences, Department of Nutritional Science, Kobe-Gakuin University High Technology Research Center, Kobe-Gakuin University
  • Sakaguchi Kengo
    Department of Applied Biological Science, Science University of Tokyo

書誌事項

タイトル別名
  • Selective Inhibition of Mammalian DNA Polymerase .ALPHA. by Vitamin D2 and D3
  • Selective Inhibition of Mammalian DNA Polymerase アルファ by Vitamin D2 and D3
公開日
2003
資源種別
journal article
DOI
  • 10.1254/jphs.92.283
公開者
公益社団法人 日本薬理学会

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説明

As described previously (H. Togashi et al. Biochem Pharmacol. 1998;56:583–590), the irradiated products of provitamin D2 (ergosterol) inhibit the activities of eukaryotic DNA polymerases. In this report, therefore, we investigated whether vitamin D and its related compounds inhibited the activities of DNA polymerases. As expected, vitamin D2 and vitamin D3 were found to be selective inhibitors of mammalian DNA polymerase α (pol α) with IC50 values of 123 and 96 μM, respectively. On the other hand, provitamin D2, provitamin D3, and the active form of vitamin D3 such as 1α,25-dihydroxyvitamin D3 could not influence any of the DNA polymerase activities. Interestingly, vitamin D3-3β-sulfate was a much stronger pol α inhibitor with an IC50 value of 7.1 μM. Vitamin D2, vitamin D3, and vitamin D3-3β-sulfate could prevent the growth of NUGC-3 human gastric cancer cells with LD50 values of 133, 77, and 44 μM, respectively, but provitamin D2 and provitamin D3 could not. The cells were halted at the G1 phase in the cell cycle by these compounds.<br>

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