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Specific effects of antitumor active norspermidine on the structure and function of DNA

We compared the effects of trivalent polyamines, spermidine (SPD) and norspermidine (NSPD), a chemical homologue of SPD, on the structure of DNA and gene expression. The chemical structures of SPD and NSPD are different only with the number of methylene groups between amine groups, [N-3-N-4-N] and [...

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Autores principales: Nishio, Takashi, Yoshikawa, Yuko, Shew, Chwen-Yang, Umezawa, Naoki, Higuchi, Tsunehiko, Yoshikawa, Kenichi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6802174/
https://www.ncbi.nlm.nih.gov/pubmed/31628357
http://dx.doi.org/10.1038/s41598-019-50943-1
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author Nishio, Takashi
Yoshikawa, Yuko
Shew, Chwen-Yang
Umezawa, Naoki
Higuchi, Tsunehiko
Yoshikawa, Kenichi
author_facet Nishio, Takashi
Yoshikawa, Yuko
Shew, Chwen-Yang
Umezawa, Naoki
Higuchi, Tsunehiko
Yoshikawa, Kenichi
author_sort Nishio, Takashi
collection PubMed
description We compared the effects of trivalent polyamines, spermidine (SPD) and norspermidine (NSPD), a chemical homologue of SPD, on the structure of DNA and gene expression. The chemical structures of SPD and NSPD are different only with the number of methylene groups between amine groups, [N-3-N-4-N] and [N-3-N-3-N], respectively. SPD plays vital roles in cell function and survival, including in mammals. On the other hand, NSPD has antitumor activity and is found in some species of plants, bacteria and algae, but not in humans. We found that both polyamines exhibit biphasic effect; enhancement and inhibition on in vitro gene expression, where SPD shows definitely higher potency in enhancement but NSPD causes stronger inhibition. Based on the results of AFM (atomic force microscopy) observations together with single DNA measurements with fluorescence microscopy, it becomes clear that SPD tends to align DNA orientation, whereas NSPD induces shrinkage with a greater potency. The measurement of binding equilibrium by NMR indicates that NSPD shows 4–5 times higher affinity to DNA than SPD. Our theoretical study with Monte Carlo simulation provides the insights into the underlying mechanism of the specific effect of NSPD on DNA.
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spelling pubmed-68021742019-10-24 Specific effects of antitumor active norspermidine on the structure and function of DNA Nishio, Takashi Yoshikawa, Yuko Shew, Chwen-Yang Umezawa, Naoki Higuchi, Tsunehiko Yoshikawa, Kenichi Sci Rep Article We compared the effects of trivalent polyamines, spermidine (SPD) and norspermidine (NSPD), a chemical homologue of SPD, on the structure of DNA and gene expression. The chemical structures of SPD and NSPD are different only with the number of methylene groups between amine groups, [N-3-N-4-N] and [N-3-N-3-N], respectively. SPD plays vital roles in cell function and survival, including in mammals. On the other hand, NSPD has antitumor activity and is found in some species of plants, bacteria and algae, but not in humans. We found that both polyamines exhibit biphasic effect; enhancement and inhibition on in vitro gene expression, where SPD shows definitely higher potency in enhancement but NSPD causes stronger inhibition. Based on the results of AFM (atomic force microscopy) observations together with single DNA measurements with fluorescence microscopy, it becomes clear that SPD tends to align DNA orientation, whereas NSPD induces shrinkage with a greater potency. The measurement of binding equilibrium by NMR indicates that NSPD shows 4–5 times higher affinity to DNA than SPD. Our theoretical study with Monte Carlo simulation provides the insights into the underlying mechanism of the specific effect of NSPD on DNA. Nature Publishing Group UK 2019-10-18 /pmc/articles/PMC6802174/ /pubmed/31628357 http://dx.doi.org/10.1038/s41598-019-50943-1 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Nishio, Takashi
Yoshikawa, Yuko
Shew, Chwen-Yang
Umezawa, Naoki
Higuchi, Tsunehiko
Yoshikawa, Kenichi
Specific effects of antitumor active norspermidine on the structure and function of DNA
title Specific effects of antitumor active norspermidine on the structure and function of DNA
title_full Specific effects of antitumor active norspermidine on the structure and function of DNA
title_fullStr Specific effects of antitumor active norspermidine on the structure and function of DNA
title_full_unstemmed Specific effects of antitumor active norspermidine on the structure and function of DNA
title_short Specific effects of antitumor active norspermidine on the structure and function of DNA
title_sort specific effects of antitumor active norspermidine on the structure and function of dna
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6802174/
https://www.ncbi.nlm.nih.gov/pubmed/31628357
http://dx.doi.org/10.1038/s41598-019-50943-1
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