The effects of dehydroaltenusin, a novel mammalian DNA polymerase alpha inhibitor, on cell proliferation and cell cycle progression

Biochimica Et Biophysica Acta
Chikako Murakami-NakaiYoshiyuki Mizushina

Abstract

As described previously, a natural product isolated from fungus (Acremonium sp.), dehydroaltenusin, is an inhibitor of mammalian DNA polymerase alpha in vitro [Y. Mizushina, S. Kamisuki, T. Mizuno, M. Takemura, H. Asahara, S. Linn, T. Yamaguchi, A. Matsukage, F. Hanaoka, S. Yoshida, M. Saneyoshi, F. Sugawara, K. Sakaguchi, Dehydroaltenusin, a mammalian DNA polymerase alpha inhibitor, J. Biol. Chem. 275 (2000) 33957_33961]. In this study, we investigated the interaction of dehydroaltenusin with lipid bilayers using an in vitro liposome system, which is a model of the cell membrane, and found that approximately 4% of dehydroaltenusin was incorporated into liposomes. We also investigated the influence of dehydroaltenusin on cultured cancer cells. Dehydroaltenusin inhibited the growth of HeLa cells with an LD50 value of 38 microM, and as expected, S phase accumulation in the cell cycle. The total DNA polymerase activity of the extract of incubated cells with dehydroaltenusin was 23% lower than that of nontreated cells. Dehydroaltenusin increased cyclin E and cyclin A levels. In the analysis of the cell cycle using G1/S synchronized cells by employing hydroxyurea, the compound delayed both entry into the S phase and S phase progress...Continue Reading

Citations

Mar 9, 2013·Bioscience, Biotechnology, and Biochemistry·Kouji Kuramochi
Apr 25, 2014·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ziling MaoLigang Zhou
Sep 20, 2011·Expert Opinion on Investigational Drugs·Yoshiyuki MizushinaHiromi Yoshida
Oct 21, 2005·Biochemical and Biophysical Research Communications·Yoshiyuki MizushinaHiromi Yoshida
Jul 9, 2011·Bioscience, Biotechnology, and Biochemistry·Masaharu TakemuraTeruyoshi Oshima
Jun 19, 2009·Chemical Reviews·Stefan BräseCarl F Nising
Jul 4, 2009·Journal of Natural Products·Martina Altemöller, Joachim Podlech

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