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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2018
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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. |
format | Online Article Text |
id | pubmed-5783490 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
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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