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Physiological Cell Culture Media Tune Mitochondrial Bioenergetics and Drug Sensitivity in Cancer Cell Models

Authors :
Omar Torres-Quesada
Carolina Doerrier
Sophie Strich
Erich Gnaiger
Eduard Stefan
Source :
Cancers; Volume 14; Issue 16; Pages: 3917
Publication Year :
2022

Abstract

Two-dimensional cell cultures are established models in research for studying and perturbing cell-type specific functions. However, many limitations apply to the cell growth in a monolayer using standard cell culture media. Although they have been used for decades, their formulations do not mimic the composition of the human cell environment. In this study, we analyzed the impact of a newly formulated human plasma-like media (HPLM) on cell proliferation, mitochondrial bioenergetics, and alterations of drug efficacies using three distinct cancer cell lines. Using high-resolution respirometry, we observed that cells grown in HPLM displayed significantly altered mitochondrial bioenergetic profiles, particularly related to mitochondrial density and mild uncoupling of respiration. Furthermore, in contrast to standard media, the growth of cells in HPLM unveiled mitochondrial dysfunction upon exposure to the FDA-approved kinase inhibitor sunitinib. This seemingly context-dependent side effect of this drug highlights that the selection of the cell culture medium influences the assessment of cancer drug sensitivities. Thus, we suggest to prioritize media with a more physiological composition for analyzing bioenergetic profiles and to take it into account for assigning drug efficacies in the cell culture model of choice.

Details

ISSN :
20726694
Volume :
14
Issue :
16
Database :
OpenAIRE
Journal :
Cancers
Accession number :
edsair.doi.dedup.....1213ecf349906e949c64cde9a85f9d8a