Portal de Periódicos da CAPES

Screening in serum-derived medium reveals differential response to compounds targeting metabolism

2023; Elsevier BV; Volume: 30; Issue: 9 Linguagem: Inglês

10.1016/j.chembiol.2023.08.007

2451-9456

Keene L. Abbott, Ahmed Ali, Dominick Casalena, T. Brian, Raphaël Ferreira, Jaime H. Cheah, Christian K. Soule, Amy Deik, Tenzin Kunchok, Daniel R. Schmidt, Steffen Renner, Sophie Honeder, Michelle Xiao Wu, Sze Ham Chan, Tenzin Tseyang, Andrew T. Stoltzfus, Sarah L. J. Michel, Daniel Greaves, Peggy P. Hsu, Christopher Ng, Chelsea J. Zhang, Ali Farsidjani, Johnathan R. Kent, Maria Lucia L. Madariaga, Iva Monique T. Gramatikov, Nicholas J. Matheson, Caroline A. Lewis, Clary B. Clish, Matthew G. Rees, Jennifer A. Roth, Lesley A. Mathews Griner, Alexander Muir, Douglas S. Auld, Matthew G. Vander Heiden,

Bioinformatics and Genomic Networks

A challenge for screening new anticancer drugs is that efficacy in cell culture models is not always predictive of efficacy in patients. One limitation of standard cell culture is a reliance on non-physiological nutrient levels, which can influence cell metabolism and drug sensitivity. A general assessment of how physiological nutrients affect cancer cell response to small molecule therapies is lacking. To address this, we developed a serum-derived culture medium that supports the proliferation of diverse cancer cell lines and is amenable to high-throughput screening. We screened several small molecule libraries and found that compounds targeting metabolic enzymes were differentially effective in standard compared to serum-derived medium. We exploited the differences in nutrient levels between each medium to understand why medium conditions affected the response of cells to some compounds, illustrating how this approach can be used to screen potential therapeutics and understand how their efficacy is modified by available nutrients.