Metabolic reprogramming is associated with flavopiridol resistance in prostate cancer DU145 cells

Abstract Flavopiridol (FP) is a pan-cyclin dependent kinase inhibitor, which shows strong efficacy in inducing cancer cell apoptosis. Although FP is potent against most cancer cells in vitro, unfortunately it proved less efficacious in clinical trials in various aggressive cancers. To date, the mole...

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Autores principales:	Xiaoran Li, Jie Lu, Quancheng Kan, Xiaoli Li, Qiong Fan, Yaqing Li, Ruixia Huang, Ana Slipicevic, Hiep Phuc Dong, Lars Eide, Junbai Wang, Hongquan Zhang, Viktor Berge, Mariusz Adam Goscinski, Gunnar Kvalheim, Jahn M. Nesland, Zhenhe Suo
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/bc89935f75804aa4884f583426b81b31
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spelling	oai:doaj.org-article:bc89935f75804aa4884f583426b81b312021-12-02T16:06:27ZMetabolic reprogramming is associated with flavopiridol resistance in prostate cancer DU145 cells10.1038/s41598-017-05086-62045-2322https://doaj.org/article/bc89935f75804aa4884f583426b81b312017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05086-6https://doaj.org/toc/2045-2322Abstract Flavopiridol (FP) is a pan-cyclin dependent kinase inhibitor, which shows strong efficacy in inducing cancer cell apoptosis. Although FP is potent against most cancer cells in vitro, unfortunately it proved less efficacious in clinical trials in various aggressive cancers. To date, the molecular mechanisms of the FP resistance are mostly unknown. Here, we report that a small fraction human prostate cancer DU145 cells can survive long-term FP treatment and emerge as FP-resistant cells (DU145FP). These DU145FP cells show accumulated mitochondrial lesions with stronger glycolytic features, and they proliferate in slow-cycling and behave highly migratory with strong anti-apoptotic potential. In addition, the cells are less sensitive to cisplatin and docetaxel-induced apoptotic pressure, and over-express multiple stem cell associated biomarkers. Our studies collectively uncover for the first time that FP-resistant prostate cancer cells show metabolic remodeling, and the metabolic plasticity might be required for the FP resistance-associated cancer cell stemness up-regulation.Xiaoran LiJie LuQuancheng KanXiaoli LiQiong FanYaqing LiRuixia HuangAna SlipicevicHiep Phuc DongLars EideJunbai WangHongquan ZhangViktor BergeMariusz Adam GoscinskiGunnar KvalheimJahn M. NeslandZhenhe SuoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-20 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xiaoran Li Jie Lu Quancheng Kan Xiaoli Li Qiong Fan Yaqing Li Ruixia Huang Ana Slipicevic Hiep Phuc Dong Lars Eide Junbai Wang Hongquan Zhang Viktor Berge Mariusz Adam Goscinski Gunnar Kvalheim Jahn M. Nesland Zhenhe Suo Metabolic reprogramming is associated with flavopiridol resistance in prostate cancer DU145 cells
description	Abstract Flavopiridol (FP) is a pan-cyclin dependent kinase inhibitor, which shows strong efficacy in inducing cancer cell apoptosis. Although FP is potent against most cancer cells in vitro, unfortunately it proved less efficacious in clinical trials in various aggressive cancers. To date, the molecular mechanisms of the FP resistance are mostly unknown. Here, we report that a small fraction human prostate cancer DU145 cells can survive long-term FP treatment and emerge as FP-resistant cells (DU145FP). These DU145FP cells show accumulated mitochondrial lesions with stronger glycolytic features, and they proliferate in slow-cycling and behave highly migratory with strong anti-apoptotic potential. In addition, the cells are less sensitive to cisplatin and docetaxel-induced apoptotic pressure, and over-express multiple stem cell associated biomarkers. Our studies collectively uncover for the first time that FP-resistant prostate cancer cells show metabolic remodeling, and the metabolic plasticity might be required for the FP resistance-associated cancer cell stemness up-regulation.
format	article
author	Xiaoran Li Jie Lu Quancheng Kan Xiaoli Li Qiong Fan Yaqing Li Ruixia Huang Ana Slipicevic Hiep Phuc Dong Lars Eide Junbai Wang Hongquan Zhang Viktor Berge Mariusz Adam Goscinski Gunnar Kvalheim Jahn M. Nesland Zhenhe Suo
author_facet	Xiaoran Li Jie Lu Quancheng Kan Xiaoli Li Qiong Fan Yaqing Li Ruixia Huang Ana Slipicevic Hiep Phuc Dong Lars Eide Junbai Wang Hongquan Zhang Viktor Berge Mariusz Adam Goscinski Gunnar Kvalheim Jahn M. Nesland Zhenhe Suo
author_sort	Xiaoran Li
title	Metabolic reprogramming is associated with flavopiridol resistance in prostate cancer DU145 cells
title_short	Metabolic reprogramming is associated with flavopiridol resistance in prostate cancer DU145 cells
title_full	Metabolic reprogramming is associated with flavopiridol resistance in prostate cancer DU145 cells
title_fullStr	Metabolic reprogramming is associated with flavopiridol resistance in prostate cancer DU145 cells
title_full_unstemmed	Metabolic reprogramming is associated with flavopiridol resistance in prostate cancer DU145 cells
title_sort	metabolic reprogramming is associated with flavopiridol resistance in prostate cancer du145 cells
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/bc89935f75804aa4884f583426b81b31
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Metabolic reprogramming is associated with flavopiridol resistance in prostate cancer DU145 cells

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