Selective Inhibition of Mammalian DNA Polymerase by Vitamin D2 and D3
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...
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doaj-54dcc86120c0422baf720575370ef8522020-11-25T01:48:51ZengElsevierJournal of Pharmacological Sciences1347-86132003-01-01923283290Selective Inhibition of Mammalian DNA Polymerase by Vitamin D2 and D3Yoshiyuki Mizushina0Xianai Xu1Chikako Murakami2Toshio Okano3Masaharu Takemura4Hiromi Yoshida5Kengo Sakaguchi6Laboratory of Food & Nutritional Sciences, Department of Nutritional Science, 2High Technology Research Center, Kobe-Gakuin University, Nishi-ku, Kobe, Hyogo 651-2180, Japan; High Technology Research Center, Kobe-Gakuin University, Nishi-ku, Kobe, Hyogo 651-2180, JapanLaboratory of Food & Nutritional Sciences, Department of Nutritional Science, 2High Technology Research Center, Kobe-Gakuin University, Nishi-ku, Kobe, Hyogo 651-2180, JapanLaboratory of Food & Nutritional Sciences, Department of Nutritional Science, 2High Technology Research Center, Kobe-Gakuin University, Nishi-ku, Kobe, Hyogo 651-2180, JapanDepartment of Hygienic Sciences, Kobe Pharmaceutical University, Higashinada-ku, Kobe, Hyogo 658-8558, JapanLaboratory of Cancer Cell Biology, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Nagoya, Aichi 466-8550, JapanLaboratory of Food & Nutritional Sciences, Department of Nutritional Science, 2High Technology Research Center, Kobe-Gakuin University, Nishi-ku, Kobe, Hyogo 651-2180, Japan; High Technology Research Center, Kobe-Gakuin University, Nishi-ku, Kobe, Hyogo 651-2180, JapanDepartment of Applied Biological Science, Science University of Tokyo, Noda, Chiba 278-8510, JapanAs 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 a (pol a) 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 1a,25-dihydroxyvitamin D3 could not influence any of the DNA polymerase activities. Interestingly, vitamin D3-3β-sulfate was a much stronger pol a 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.http://www.sciencedirect.com/science/article/pii/S134786131932660X |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yoshiyuki Mizushina Xianai Xu Chikako Murakami Toshio Okano Masaharu Takemura Hiromi Yoshida Kengo Sakaguchi |
spellingShingle |
Yoshiyuki Mizushina Xianai Xu Chikako Murakami Toshio Okano Masaharu Takemura Hiromi Yoshida Kengo Sakaguchi Selective Inhibition of Mammalian DNA Polymerase by Vitamin D2 and D3 Journal of Pharmacological Sciences |
author_facet |
Yoshiyuki Mizushina Xianai Xu Chikako Murakami Toshio Okano Masaharu Takemura Hiromi Yoshida Kengo Sakaguchi |
author_sort |
Yoshiyuki Mizushina |
title |
Selective Inhibition of Mammalian DNA Polymerase by Vitamin D2 and D3 |
title_short |
Selective Inhibition of Mammalian DNA Polymerase by Vitamin D2 and D3 |
title_full |
Selective Inhibition of Mammalian DNA Polymerase by Vitamin D2 and D3 |
title_fullStr |
Selective Inhibition of Mammalian DNA Polymerase by Vitamin D2 and D3 |
title_full_unstemmed |
Selective Inhibition of Mammalian DNA Polymerase by Vitamin D2 and D3 |
title_sort |
selective inhibition of mammalian dna polymerase by vitamin d2 and d3 |
publisher |
Elsevier |
series |
Journal of Pharmacological Sciences |
issn |
1347-8613 |
publishDate |
2003-01-01 |
description |
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 a (pol a) 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 1a,25-dihydroxyvitamin D3 could not influence any of the DNA polymerase activities. Interestingly, vitamin D3-3β-sulfate was a much stronger pol a 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. |
url |
http://www.sciencedirect.com/science/article/pii/S134786131932660X |
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