Selective Inhibition of Mammalian DNA Polymerase α by Vitamin D_2 and D_3

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Author(s)

Abstract

As described previously (H. Togashi et al. Biochem Pharmacol. 1998;56:583–590), the irradiated products of provitamin D<sub>2</sub> (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 D<sub>2</sub> and vitamin D<sub>3</sub> were found to be selective inhibitors of mammalian DNA polymerase α (pol α) with IC<sub>50</sub> values of 123 and 96 μM, respectively. On the other hand, provitamin D<sub>2</sub>, provitamin D<sub>3</sub>, and the active form of vitamin D<sub>3</sub> such as 1α,25-dihydroxyvitamin D<sub>3</sub> could not influence any of the DNA polymerase activities. Interestingly, vitamin D<sub>3</sub>-3β-sulfate was a much stronger pol α inhibitor with an IC<sub>50</sub> value of 7.1 μM. Vitamin D<sub>2</sub>, vitamin D<sub>3</sub>, and vitamin D<sub>3</sub>-3β-sulfate could prevent the growth of NUGC-3 human gastric cancer cells with LD<sub>50</sub> values of 133, 77, and 44 μM, respectively, but provitamin D<sub>2</sub> and provitamin D<sub>3</sub> could not. The cells were halted at the G1 phase in the cell cycle by these compounds.<br>

Journal

  • Journal of Pharmacological Sciences

    Journal of Pharmacological Sciences 92(3), 283-290, 2003-07-01

    The Japanese Pharmacological Society

References:  33

Cited by:  1

Codes

  • NII Article ID (NAID)
    10011209806
  • NII NACSIS-CAT ID (NCID)
    AA11806667
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    13478613
  • NDL Article ID
    6614426
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  CJPref  NDL  J-STAGE 
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