Danazol mediates collateral sensitivity via STAT3/Myc related pathway in multidrug-resistant cancer cells

Abstract Multidrug resistance presents an obstacle in cancer treatment. Among numerous combative strategies, collateral sensitivity (CS) drugs have opened a new avenue to defeat cancer by exploiting selective toxicity against multidrug-resistant (MDR) cancer. In the present study, a clinically used...

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Autores principales:	Ying-Tzu Chang, Yu-Ning Teng, Kun-I Lin, Charles C. N. Wang, Susan L. Morris-Natschke, Kuo-Hsiung Lee, Chin-Chuan Hung
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/aadb4fb6502e4754853b555fcbdbf894
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spelling	oai:doaj.org-article:aadb4fb6502e4754853b555fcbdbf8942021-12-02T15:09:22ZDanazol mediates collateral sensitivity via STAT3/Myc related pathway in multidrug-resistant cancer cells10.1038/s41598-019-48169-22045-2322https://doaj.org/article/aadb4fb6502e4754853b555fcbdbf8942019-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-48169-2https://doaj.org/toc/2045-2322Abstract Multidrug resistance presents an obstacle in cancer treatment. Among numerous combative strategies, collateral sensitivity (CS) drugs have opened a new avenue to defeat cancer by exploiting selective toxicity against multidrug-resistant (MDR) cancer. In the present study, a clinically used synthetic steroid hormone, danazol, was investigated for its CS properties and cytotoxic mechanisms. Compared with natural hormones, danazol possessed a stronger selective cytotoxicity against MDR cancer cells. Danazol induced the arrest of MDR cancer cells at the G2/M phase and caspase-8–related early apoptosis. Furthermore, in MDR cancer cells, danazol reduced STAT3 phosphorylation as well as the expression of STAT3-regulated genes involved in cell survival, such as c-Myc, CDC25, and CDK1. Danazol also upregulated the cell cycle inhibitor p21 in MDR cancer cells. Supporting the experimental results, docking studies have revealed that danazol can likely bind favourably with STAT3. Taken together, our results suggest that danazol exerts a CS effect by inhibiting the STAT3 pathway in MDR cancer cells and thus provides a possible solution for MDR cancers.Ying-Tzu ChangYu-Ning TengKun-I LinCharles C. N. WangSusan L. Morris-NatschkeKuo-Hsiung LeeChin-Chuan HungNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-11 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ying-Tzu Chang Yu-Ning Teng Kun-I Lin Charles C. N. Wang Susan L. Morris-Natschke Kuo-Hsiung Lee Chin-Chuan Hung Danazol mediates collateral sensitivity via STAT3/Myc related pathway in multidrug-resistant cancer cells
description	Abstract Multidrug resistance presents an obstacle in cancer treatment. Among numerous combative strategies, collateral sensitivity (CS) drugs have opened a new avenue to defeat cancer by exploiting selective toxicity against multidrug-resistant (MDR) cancer. In the present study, a clinically used synthetic steroid hormone, danazol, was investigated for its CS properties and cytotoxic mechanisms. Compared with natural hormones, danazol possessed a stronger selective cytotoxicity against MDR cancer cells. Danazol induced the arrest of MDR cancer cells at the G2/M phase and caspase-8–related early apoptosis. Furthermore, in MDR cancer cells, danazol reduced STAT3 phosphorylation as well as the expression of STAT3-regulated genes involved in cell survival, such as c-Myc, CDC25, and CDK1. Danazol also upregulated the cell cycle inhibitor p21 in MDR cancer cells. Supporting the experimental results, docking studies have revealed that danazol can likely bind favourably with STAT3. Taken together, our results suggest that danazol exerts a CS effect by inhibiting the STAT3 pathway in MDR cancer cells and thus provides a possible solution for MDR cancers.
format	article
author	Ying-Tzu Chang Yu-Ning Teng Kun-I Lin Charles C. N. Wang Susan L. Morris-Natschke Kuo-Hsiung Lee Chin-Chuan Hung
author_facet	Ying-Tzu Chang Yu-Ning Teng Kun-I Lin Charles C. N. Wang Susan L. Morris-Natschke Kuo-Hsiung Lee Chin-Chuan Hung
author_sort	Ying-Tzu Chang
title	Danazol mediates collateral sensitivity via STAT3/Myc related pathway in multidrug-resistant cancer cells
title_short	Danazol mediates collateral sensitivity via STAT3/Myc related pathway in multidrug-resistant cancer cells
title_full	Danazol mediates collateral sensitivity via STAT3/Myc related pathway in multidrug-resistant cancer cells
title_fullStr	Danazol mediates collateral sensitivity via STAT3/Myc related pathway in multidrug-resistant cancer cells
title_full_unstemmed	Danazol mediates collateral sensitivity via STAT3/Myc related pathway in multidrug-resistant cancer cells
title_sort	danazol mediates collateral sensitivity via stat3/myc related pathway in multidrug-resistant cancer cells
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/aadb4fb6502e4754853b555fcbdbf894
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Danazol mediates collateral sensitivity via STAT3/Myc related pathway in multidrug-resistant cancer cells

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