Schisandrin B reverses doxorubicin resistance through inhibiting P-glycoprotein and promoting proteasome-mediated degradation of survivin

Abstract Acquired drug resistance poses a great challenge in cancer therapy. Drug efflux and anti-apoptotic processes are the most two common mechanisms that confer cancer drug resistance. In this study, we found that Schisandrin B (Sch B), one of the major dibenzocyclooctadiene derivatives extracte...

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Autores principales:	Shengpeng Wang, Anqi Wang, Min Shao, Ligen Lin, Peng Li, Yitao Wang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/99fd5d17a44840458986437688e03c12
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spelling	oai:doaj.org-article:99fd5d17a44840458986437688e03c122021-12-02T12:32:06ZSchisandrin B reverses doxorubicin resistance through inhibiting P-glycoprotein and promoting proteasome-mediated degradation of survivin10.1038/s41598-017-08817-x2045-2322https://doaj.org/article/99fd5d17a44840458986437688e03c122017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08817-xhttps://doaj.org/toc/2045-2322Abstract Acquired drug resistance poses a great challenge in cancer therapy. Drug efflux and anti-apoptotic processes are the most two common mechanisms that confer cancer drug resistance. In this study, we found that Schisandrin B (Sch B), one of the major dibenzocyclooctadiene derivatives extracted from Chinese herbal medicine Schisandrae Chinensis Fructus, could significantly enhance the sensitivity of doxorubicin (DOX)-resistant breast cancer and ovarian cancer cells to DOX. Our results showed that Sch B increased the intracellular accumulation of DOX through inhibiting expression and activity of P-glycoprotein (P-gp). Meanwhile, Sch B could markedly downregulate the expression of anti-apoptotic protein survivin. Overexpression of survivin attenuated the sensitizing effects of Sch B, while silencing of survivin enhanced Sch B-mediated sensitizing effects. Furthermore, Sch B preferentially promoted chymotryptic activity of the proteasome in a concentration-dependent manner, and the proteasome inhibitor MG-132 prevented Sch B-induced survivin downregulation. Taken together, our findings suggest that Sch B could be a potential candidate for combating drug resistant cancer via modulating two key factors that responsible for cancer resistance.Shengpeng WangAnqi WangMin ShaoLigen LinPeng LiYitao WangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shengpeng Wang Anqi Wang Min Shao Ligen Lin Peng Li Yitao Wang Schisandrin B reverses doxorubicin resistance through inhibiting P-glycoprotein and promoting proteasome-mediated degradation of survivin
description	Abstract Acquired drug resistance poses a great challenge in cancer therapy. Drug efflux and anti-apoptotic processes are the most two common mechanisms that confer cancer drug resistance. In this study, we found that Schisandrin B (Sch B), one of the major dibenzocyclooctadiene derivatives extracted from Chinese herbal medicine Schisandrae Chinensis Fructus, could significantly enhance the sensitivity of doxorubicin (DOX)-resistant breast cancer and ovarian cancer cells to DOX. Our results showed that Sch B increased the intracellular accumulation of DOX through inhibiting expression and activity of P-glycoprotein (P-gp). Meanwhile, Sch B could markedly downregulate the expression of anti-apoptotic protein survivin. Overexpression of survivin attenuated the sensitizing effects of Sch B, while silencing of survivin enhanced Sch B-mediated sensitizing effects. Furthermore, Sch B preferentially promoted chymotryptic activity of the proteasome in a concentration-dependent manner, and the proteasome inhibitor MG-132 prevented Sch B-induced survivin downregulation. Taken together, our findings suggest that Sch B could be a potential candidate for combating drug resistant cancer via modulating two key factors that responsible for cancer resistance.
format	article
author	Shengpeng Wang Anqi Wang Min Shao Ligen Lin Peng Li Yitao Wang
author_facet	Shengpeng Wang Anqi Wang Min Shao Ligen Lin Peng Li Yitao Wang
author_sort	Shengpeng Wang
title	Schisandrin B reverses doxorubicin resistance through inhibiting P-glycoprotein and promoting proteasome-mediated degradation of survivin
title_short	Schisandrin B reverses doxorubicin resistance through inhibiting P-glycoprotein and promoting proteasome-mediated degradation of survivin
title_full	Schisandrin B reverses doxorubicin resistance through inhibiting P-glycoprotein and promoting proteasome-mediated degradation of survivin
title_fullStr	Schisandrin B reverses doxorubicin resistance through inhibiting P-glycoprotein and promoting proteasome-mediated degradation of survivin
title_full_unstemmed	Schisandrin B reverses doxorubicin resistance through inhibiting P-glycoprotein and promoting proteasome-mediated degradation of survivin
title_sort	schisandrin b reverses doxorubicin resistance through inhibiting p-glycoprotein and promoting proteasome-mediated degradation of survivin
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/99fd5d17a44840458986437688e03c12
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Schisandrin B reverses doxorubicin resistance through inhibiting P-glycoprotein and promoting proteasome-mediated degradation of survivin

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