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Tan IIA inhibits H1299 cell viability through the MDM4-IAP3 signaling pathway

Tanshinone IIA (Tan IIA), as a bioactive compound extracted from the dried roots of Salvia miltiorrhiza (also known as Danshen), is known to inhibit cancer cell proliferation and induce apoptosis. However, the mechanisms underlying the function of Tan IIA in cancer cell apoptosis remain to be elucid...

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Autores principales: Zu, Yukun, Wang, Jianning, Ping, Wei, Sun, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5783490/
https://www.ncbi.nlm.nih.gov/pubmed/29207086
http://dx.doi.org/10.3892/mmr.2017.8152
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author Zu, Yukun
Wang, Jianning
Ping, Wei
Sun, Wei
author_facet Zu, Yukun
Wang, Jianning
Ping, Wei
Sun, Wei
author_sort Zu, Yukun
collection PubMed
description Tanshinone IIA (Tan IIA), as a bioactive compound extracted from the dried roots of Salvia miltiorrhiza (also known as Danshen), is known to inhibit cancer cell proliferation and induce apoptosis. However, the mechanisms underlying the function of Tan IIA in cancer cell apoptosis remain to be elucidated The aim of the present study was to identify the molecular mechanisms underlying the anti-cancer effects of Tan IIA in p53-deficient H1299 cells. Tan IIA was demonstrated to suppress murine double minute 4 (MDM4) expression in a time- and dose-dependent manner through the inhibition of MDM4 mRNA synthesis. Tan IIA-induced downregulation of MDM4 resulted in an increase of P73α and a decrease of inhibitor of apoptosis 3 (IAP3). However, P73α was not activated as two P73α target genes, BCL2 binding component 3 and phorbol-12-myristate-13-acetate-induced protein 1, were not significantly induced. Tan IIA-induced inhibition of IAP3 expression may be involved in Tan IIA-induced apoptosis and inhibition of H1299 cell viability. Notably, a combination of Tan IIA and doxorubicin (DOX) exposure resulted in further MDM4 overexpression in H1299 cells, indicating that Tan IIA sensitized p53-deficient and MDM4-overexpressing H1299 cells to DOX-induced apoptosis.
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spelling pubmed-57834902018-02-05 Tan IIA inhibits H1299 cell viability through the MDM4-IAP3 signaling pathway Zu, Yukun Wang, Jianning Ping, Wei Sun, Wei Mol Med Rep Articles Tanshinone IIA (Tan IIA), as a bioactive compound extracted from the dried roots of Salvia miltiorrhiza (also known as Danshen), is known to inhibit cancer cell proliferation and induce apoptosis. However, the mechanisms underlying the function of Tan IIA in cancer cell apoptosis remain to be elucidated The aim of the present study was to identify the molecular mechanisms underlying the anti-cancer effects of Tan IIA in p53-deficient H1299 cells. Tan IIA was demonstrated to suppress murine double minute 4 (MDM4) expression in a time- and dose-dependent manner through the inhibition of MDM4 mRNA synthesis. Tan IIA-induced downregulation of MDM4 resulted in an increase of P73α and a decrease of inhibitor of apoptosis 3 (IAP3). However, P73α was not activated as two P73α target genes, BCL2 binding component 3 and phorbol-12-myristate-13-acetate-induced protein 1, were not significantly induced. Tan IIA-induced inhibition of IAP3 expression may be involved in Tan IIA-induced apoptosis and inhibition of H1299 cell viability. Notably, a combination of Tan IIA and doxorubicin (DOX) exposure resulted in further MDM4 overexpression in H1299 cells, indicating that Tan IIA sensitized p53-deficient and MDM4-overexpressing H1299 cells to DOX-induced apoptosis. D.A. Spandidos 2018-02 2017-11-24 /pmc/articles/PMC5783490/ /pubmed/29207086 http://dx.doi.org/10.3892/mmr.2017.8152 Text en Copyright: © Zu et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Zu, Yukun
Wang, Jianning
Ping, Wei
Sun, Wei
Tan IIA inhibits H1299 cell viability through the MDM4-IAP3 signaling pathway
title Tan IIA inhibits H1299 cell viability through the MDM4-IAP3 signaling pathway
title_full Tan IIA inhibits H1299 cell viability through the MDM4-IAP3 signaling pathway
title_fullStr Tan IIA inhibits H1299 cell viability through the MDM4-IAP3 signaling pathway
title_full_unstemmed Tan IIA inhibits H1299 cell viability through the MDM4-IAP3 signaling pathway
title_short Tan IIA inhibits H1299 cell viability through the MDM4-IAP3 signaling pathway
title_sort tan iia inhibits h1299 cell viability through the mdm4-iap3 signaling pathway
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5783490/
https://www.ncbi.nlm.nih.gov/pubmed/29207086
http://dx.doi.org/10.3892/mmr.2017.8152
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