Echinacoside induces apoptotic cancer cell death by inhibiting the nucleotide pool sanitizing enzyme MTH1

Inhibition of the nucleotide pool sanitizing enzyme MTH1 causes extensive oxidative DNA damages and apoptosis in cancer cells and hence may be used as an anticancer strategy. As natural products have been a rich source of medicinal chemicals, in the present study, we used the MTH1-catalyzed enzymati...

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Main Authors:	Dong, Liwei, Wang, Hongge, Niu, Jiajing, Zou, Mingwei, Wu, Nuoting, Yu, Debin, Wang, Ye, Zou, Zhihua
Format:	Online
Language:	English
Published:	Dove Medical Press 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4677763/

id	pubmed-4677763
recordtype	oai_dc
spelling	pubmed-46777632015-12-16 Echinacoside induces apoptotic cancer cell death by inhibiting the nucleotide pool sanitizing enzyme MTH1 Dong, Liwei Wang, Hongge Niu, Jiajing Zou, Mingwei Wu, Nuoting Yu, Debin Wang, Ye Zou, Zhihua Original Research Inhibition of the nucleotide pool sanitizing enzyme MTH1 causes extensive oxidative DNA damages and apoptosis in cancer cells and hence may be used as an anticancer strategy. As natural products have been a rich source of medicinal chemicals, in the present study, we used the MTH1-catalyzed enzymatic reaction as a high-throughput in vitro screening assay to search for natural compounds capable of inhibiting MTH1. Echinacoside, a compound derived from the medicinal plants Cistanche and Echinacea, effectively inhibited the catalytic activity of MTH1 in an in vitro assay. Treatment of various human cancer cell lines with Echinacoside resulted in a significant increase in the cellular level of oxidized guanine (8-oxoguanine), while cellular reactive oxygen species level remained unchanged, indicating that Echinacoside also inhibited the activity of cellular MTH1. Consequently, Echinacoside treatment induced an immediate and dramatic increase in DNA damage markers and upregulation of the G1/S-CDK inhibitor p21, which were followed by marked apoptotic cell death and cell cycle arrest in cancer but not in noncancer cells. Taken together, these studies identified a natural compound as an MTH1 inhibitor and suggest that natural products can be an important source of anticancer agents. Dove Medical Press 2015-12-08 /pmc/articles/PMC4677763/ /pubmed/26677335 http://dx.doi.org/10.2147/OTT.S94513 Text en © 2015 Dong et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Dong, Liwei Wang, Hongge Niu, Jiajing Zou, Mingwei Wu, Nuoting Yu, Debin Wang, Ye Zou, Zhihua
spellingShingle	Dong, Liwei Wang, Hongge Niu, Jiajing Zou, Mingwei Wu, Nuoting Yu, Debin Wang, Ye Zou, Zhihua Echinacoside induces apoptotic cancer cell death by inhibiting the nucleotide pool sanitizing enzyme MTH1
author_facet	Dong, Liwei Wang, Hongge Niu, Jiajing Zou, Mingwei Wu, Nuoting Yu, Debin Wang, Ye Zou, Zhihua
author_sort	Dong, Liwei
title	Echinacoside induces apoptotic cancer cell death by inhibiting the nucleotide pool sanitizing enzyme MTH1
title_short	Echinacoside induces apoptotic cancer cell death by inhibiting the nucleotide pool sanitizing enzyme MTH1
title_full	Echinacoside induces apoptotic cancer cell death by inhibiting the nucleotide pool sanitizing enzyme MTH1
title_fullStr	Echinacoside induces apoptotic cancer cell death by inhibiting the nucleotide pool sanitizing enzyme MTH1
title_full_unstemmed	Echinacoside induces apoptotic cancer cell death by inhibiting the nucleotide pool sanitizing enzyme MTH1
title_sort	echinacoside induces apoptotic cancer cell death by inhibiting the nucleotide pool sanitizing enzyme mth1
description	Inhibition of the nucleotide pool sanitizing enzyme MTH1 causes extensive oxidative DNA damages and apoptosis in cancer cells and hence may be used as an anticancer strategy. As natural products have been a rich source of medicinal chemicals, in the present study, we used the MTH1-catalyzed enzymatic reaction as a high-throughput in vitro screening assay to search for natural compounds capable of inhibiting MTH1. Echinacoside, a compound derived from the medicinal plants Cistanche and Echinacea, effectively inhibited the catalytic activity of MTH1 in an in vitro assay. Treatment of various human cancer cell lines with Echinacoside resulted in a significant increase in the cellular level of oxidized guanine (8-oxoguanine), while cellular reactive oxygen species level remained unchanged, indicating that Echinacoside also inhibited the activity of cellular MTH1. Consequently, Echinacoside treatment induced an immediate and dramatic increase in DNA damage markers and upregulation of the G1/S-CDK inhibitor p21, which were followed by marked apoptotic cell death and cell cycle arrest in cancer but not in noncancer cells. Taken together, these studies identified a natural compound as an MTH1 inhibitor and suggest that natural products can be an important source of anticancer agents.
publisher	Dove Medical Press
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4677763/
_version_	1613512537273270272

Echinacoside induces apoptotic cancer cell death by inhibiting the nucleotide pool sanitizing enzyme MTH1

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