Doxycycline impairs mitochondrial dunction and protects human glioma cells from hypoxia-induced cell death : implications of using tet-inducible systems

  • Inducible gene expression is an important tool in molecular biology research to study protein function. Most frequently, the antibiotic doxycycline is used for regulation of so-called tetracycline (Tet)-inducible systems. In contrast to stable gene overexpression, these systems allow investigation of acute and reversible effects of cellular protein induction. Recent reports have already called for caution when using Tet-inducible systems as the employed antibiotics can disturb mitochondrial function and alter cellular metabolism by interfering with mitochondrial translation. Reprogramming of energy metabolism has lately been recognized as an important emerging hallmark of cancer and is a central focus of cancer research. Therefore, the scope of this study was to systematically analyze dose-dependent metabolic effects of doxycycline on a panel of glioma cell lines with concomitant monitoring of gene expression from Tet-inducible systems. We report that doxycycline doses commonly used with inducible expression systems (0.01–1 µg/mL) substantially alter cellular metabolism: Mitochondrial protein synthesis was inhibited accompanied by reduced oxygen and increased glucose consumption. Furthermore, doxycycline protected human glioma cells from hypoxia-induced cell death. An impairment of cell growth was only detectable with higher doxycycline doses (10 µg/mL). Our findings describe settings where doxycycline exerts effects on eukaryotic cellular metabolism, limiting the employment of Tet-inducible systems.

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Author:Anna-Luisa LugerORCiD, Benedikt Sauer, Nadja Irene LorenzGND, Anna Larissa EngelGND, Yannick Braun, Martin VossORCiD, Patrick Nikolaus HarterORCiDGND, Joachim Peter SteinbachORCiDGND, Michael Wilfried RonellenfitschORCiDGND
Pubmed Id:
Parent Title (English):International journal of molecular sciences
Publisher:Molecular Diversity Preservation International
Place of publication:Basel
Document Type:Article
Year of Completion:2018
Date of first Publication:2018/05/17
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2018/06/12
Tag:Tet-inducible system; doxycycline; glioblastoma; hypoxia-induced cell death; inducible gene expression; mitochondria; tetracycline; tumor metabolism
Issue:5, Art. 1504
Page Number:17
First Page:1
Last Page:17
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0