title: Selective inhibition of mammalian DNA polymerase alpha by vitamin D2 and D3.
abstract: As described previously (H. Togashi et al. Biochem Pharmacol. 1998;56:583-590), the irradiated products of provitamin D(2) (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(2) and vitamin D(3) were found to be selective inhibitors of mammalian DNA polymerase alpha (pol alpha) with IC(50) values of 123 and 96 micro M, respectively. On the other hand, provitamin D(2), provitamin D(3), and the active form of vitamin D(3) such as 1alpha,25-dihydroxyvitamin D(3) could not influence any of the DNA polymerase activities. Interestingly, vitamin D(3)-3beta-sulfate was a much stronger pol alpha inhibitor with an IC(50) value of 7.1 micro M. Vitamin D(2), vitamin D(3), and vitamin D(3)-3beta-sulfate could prevent the growth of NUGC-3 human gastric cancer cells with LD(50) values of 133, 77, and 44 micro M, respectively, but provitamin D(2) and provitamin D(3) could not. The cells were halted at the G1 phase in the cell cycle by these compounds.
authors.affiliation: Laboratory of Food & Nutritional Sciences, Department of Nutritional Science, Kobe-Gakuin University, Hyogo, Japan. mizushin@nutr.kobegakuin.ac.jp
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Mizushina
authors.forename: Xianai
authors.initials: X
authors.lastname: Xu
authors.forename: Chikako
authors.initials: C
authors.lastname: Murakami
authors.forename: Toshio
authors.initials: T
authors.lastname: Okano
authors.forename: Masaharu
authors.initials: M
authors.lastname: Takemura
authors.forename: Hiromi
authors.initials: H
authors.lastname: Yoshida
authors.forename: Kengo
authors.initials: K
authors.lastname: Sakaguchi
mesh_terms: D000818:Animals; D002417:Cattle; D045744:Cell Line, Tumor; D002762:Cholecalciferol / Q000494:pharmacology*; D004256:DNA Polymerase I / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004872:Ergocalciferols / Q000494:pharmacology*; D006801:Humans; D051381:Rats
chemical_list: D004791:Enzyme Inhibitors; D004872:Ergocalciferols; D002762:Cholecalciferol; D004256:DNA Polymerase I