Golden berry 4β-hydroxywithanolide E prevents tumor necrosis factor α-induced procoagulant activity with enhanced cytotoxicity against human lung cancer cells

Abstract Inflammation in the tumor microenvironment is positively correlated with cancer progression and metastasis as well as the risk of thromboembolism in lung cancer patients. Here we show, in human non-small cell lung cancer (NSCLC) cell lines, the master inflammatory cytokine tumor necrosis fa...

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Autores principales:	Kan-Yen Hsieh, Ju-Ying Tsai, Ya-Han Lin, Fang-Rong Chang, Hui-Chun Wang, Chin-Chung Wu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/bd2ff2586e864342863c0a46495a5ab0
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spelling	oai:doaj.org-article:bd2ff2586e864342863c0a46495a5ab02021-12-02T15:54:09ZGolden berry 4β-hydroxywithanolide E prevents tumor necrosis factor α-induced procoagulant activity with enhanced cytotoxicity against human lung cancer cells10.1038/s41598-021-84207-82045-2322https://doaj.org/article/bd2ff2586e864342863c0a46495a5ab02021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84207-8https://doaj.org/toc/2045-2322Abstract Inflammation in the tumor microenvironment is positively correlated with cancer progression and metastasis as well as the risk of thromboembolism in lung cancer patients. Here we show, in human non-small cell lung cancer (NSCLC) cell lines, the master inflammatory cytokine tumor necrosis factor (TNF-α) induced tissue factor expression and procoagulant activity, and these effects were potently inhibited by 4β-hydroxywithanolide E (4HW), a natural compound isolated from Physalis peruviana. Furthermore, combination of 4HW and TNF-α caused synergistic cytotoxicity against NSCLC cells by inducing caspase-dependent apoptosis. The underlying mechanism by which 4HW reverses the procoagulant effect of TNF-α but enhances its cytotoxic effect appears to be due to inhibition of NF-κB, which is a key switch for both inflammation-induced coagulation and cell survival. Our results suggest that 4HW may have a potential application for treating inflammation-derived cancer progression and cancer-associated hypercoagulable state.Kan-Yen HsiehJu-Ying TsaiYa-Han LinFang-Rong ChangHui-Chun WangChin-Chung WuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kan-Yen Hsieh Ju-Ying Tsai Ya-Han Lin Fang-Rong Chang Hui-Chun Wang Chin-Chung Wu Golden berry 4β-hydroxywithanolide E prevents tumor necrosis factor α-induced procoagulant activity with enhanced cytotoxicity against human lung cancer cells
description	Abstract Inflammation in the tumor microenvironment is positively correlated with cancer progression and metastasis as well as the risk of thromboembolism in lung cancer patients. Here we show, in human non-small cell lung cancer (NSCLC) cell lines, the master inflammatory cytokine tumor necrosis factor (TNF-α) induced tissue factor expression and procoagulant activity, and these effects were potently inhibited by 4β-hydroxywithanolide E (4HW), a natural compound isolated from Physalis peruviana. Furthermore, combination of 4HW and TNF-α caused synergistic cytotoxicity against NSCLC cells by inducing caspase-dependent apoptosis. The underlying mechanism by which 4HW reverses the procoagulant effect of TNF-α but enhances its cytotoxic effect appears to be due to inhibition of NF-κB, which is a key switch for both inflammation-induced coagulation and cell survival. Our results suggest that 4HW may have a potential application for treating inflammation-derived cancer progression and cancer-associated hypercoagulable state.
format	article
author	Kan-Yen Hsieh Ju-Ying Tsai Ya-Han Lin Fang-Rong Chang Hui-Chun Wang Chin-Chung Wu
author_facet	Kan-Yen Hsieh Ju-Ying Tsai Ya-Han Lin Fang-Rong Chang Hui-Chun Wang Chin-Chung Wu
author_sort	Kan-Yen Hsieh
title	Golden berry 4β-hydroxywithanolide E prevents tumor necrosis factor α-induced procoagulant activity with enhanced cytotoxicity against human lung cancer cells
title_short	Golden berry 4β-hydroxywithanolide E prevents tumor necrosis factor α-induced procoagulant activity with enhanced cytotoxicity against human lung cancer cells
title_full	Golden berry 4β-hydroxywithanolide E prevents tumor necrosis factor α-induced procoagulant activity with enhanced cytotoxicity against human lung cancer cells
title_fullStr	Golden berry 4β-hydroxywithanolide E prevents tumor necrosis factor α-induced procoagulant activity with enhanced cytotoxicity against human lung cancer cells
title_full_unstemmed	Golden berry 4β-hydroxywithanolide E prevents tumor necrosis factor α-induced procoagulant activity with enhanced cytotoxicity against human lung cancer cells
title_sort	golden berry 4β-hydroxywithanolide e prevents tumor necrosis factor α-induced procoagulant activity with enhanced cytotoxicity against human lung cancer cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/bd2ff2586e864342863c0a46495a5ab0
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Golden berry 4β-hydroxywithanolide E prevents tumor necrosis factor α-induced procoagulant activity with enhanced cytotoxicity against human lung cancer cells

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