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

Abstract 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...

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Autores principales:	Takashi Nishio, Yuko Yoshikawa, Chwen-Yang Shew, Naoki Umezawa, Tsunehiko Higuchi, Kenichi Yoshikawa
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/23d3c11640e24d888c02bbdcafe5eba0
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spelling	oai:doaj.org-article:23d3c11640e24d888c02bbdcafe5eba02021-12-02T15:09:49ZSpecific effects of antitumor active norspermidine on the structure and function of DNA10.1038/s41598-019-50943-12045-2322https://doaj.org/article/23d3c11640e24d888c02bbdcafe5eba02019-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-50943-1https://doaj.org/toc/2045-2322Abstract 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.Takashi NishioYuko YoshikawaChwen-Yang ShewNaoki UmezawaTsunehiko HiguchiKenichi YoshikawaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-12 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Takashi Nishio Yuko Yoshikawa Chwen-Yang Shew Naoki Umezawa Tsunehiko Higuchi Kenichi Yoshikawa Specific effects of antitumor active norspermidine on the structure and function of DNA
description	Abstract 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.
format	article
author	Takashi Nishio Yuko Yoshikawa Chwen-Yang Shew Naoki Umezawa Tsunehiko Higuchi Kenichi Yoshikawa
author_facet	Takashi Nishio Yuko Yoshikawa Chwen-Yang Shew Naoki Umezawa Tsunehiko Higuchi Kenichi Yoshikawa
author_sort	Takashi Nishio
title	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_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_sort	specific effects of antitumor active norspermidine on the structure and function of dna
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/23d3c11640e24d888c02bbdcafe5eba0
work_keys_str_mv	AT takashinishio specificeffectsofantitumoractivenorspermidineonthestructureandfunctionofdna AT yukoyoshikawa specificeffectsofantitumoractivenorspermidineonthestructureandfunctionofdna AT chwenyangshew specificeffectsofantitumoractivenorspermidineonthestructureandfunctionofdna AT naokiumezawa specificeffectsofantitumoractivenorspermidineonthestructureandfunctionofdna AT tsunehikohiguchi specificeffectsofantitumoractivenorspermidineonthestructureandfunctionofdna AT kenichiyoshikawa specificeffectsofantitumoractivenorspermidineonthestructureandfunctionofdna
_version_	1718387739872722944

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

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