title: Doxycycline alters metabolism and proliferation of human cell lines.
abstract: The tetracycline antibiotics are widely used in biomedical research as mediators of inducible gene expression systems. Despite many known effects of tetracyclines on mammalian cells-including inhibition of the mitochondrial ribosome-there have been few reports on potential off-target effects at concentrations commonly used in inducible systems. Here, we report that in human cell lines, commonly used concentrations of doxycycline change gene expression patterns and concomitantly shift metabolism towards a more glycolytic phenotype, evidenced by increased lactate secretion and reduced oxygen consumption. We also show that these concentrations are sufficient to slow proliferation. These findings suggest that researchers using doxycycline in inducible expression systems should design appropriate controls to account for potential confounding effects of the drug on cellular metabolism.
authors.affiliation: Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Ethan
authors.initials: E
authors.lastname: Ahler
authors.forename: William J
authors.initials: WJ
authors.lastname: Sullivan
authors.forename: Ashley
authors.initials: A
authors.lastname: Cass
authors.forename: Daniel
authors.initials: D
authors.lastname: Braas
authors.forename: Autumn G
authors.initials: AG
authors.lastname: York
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Bensinger
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Graeber
authors.forename: Heather R
authors.initials: HR
authors.lastname: Christofk
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004318:Doxycycline / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D053858:Metabolic Networks and Pathways / Q000187:drug effects* / Q000235:genetics; D055442:Metabolome / Q000187:drug effects* / Q000235:genetics; D010101:Oxygen Consumption / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D004318:Doxycycline