In Vitro Cell Death Determination for Drug Discovery: A Landscape Review of Real Issues

Méry, Benoite; Guy, Jean-Baptiste; Vallard, Alexis; Espenel, Sophie; Ardail, Dominique; Rodriguez-Lafrasse, Claire; Rancoule, Chloé; Magné, Nicolas

The assessment of new potential chemotherapeutics and drug screening involve cell viability and cytotoxicity assays to identify and define safety thresholds for subsequent clinical use. Such assays rely on several cell functions, including enzyme activity, cell membrane activity, cell adherence, adenosine triphosphate (ATP) production, coenzyme production, and nucleotide uptake activity. If a compound interferes with cellular attachment, causes dramatic morphologic changes, affects cell growth rate, or leads to a reduction in overall viability, it is considered to be cytotoxic. 19 However, cytotoxicity reflects the cell-killing property of a chemical compound and is not associated with a specific cell death pathway. Cell viability can be defined as the number of healthy cells in a sample, without any distinction between cells which are actively dividing or quiescent ones, whereas cell proliferation is the measurement of the Méry et al 3 number of cells that are dividing in a culture. Viability assays aim to measure cellular maintenance and survival parameters. Thereby, a myriad of assays have been designed and used so as to measure viability or cytotoxicity in vitro, including, in particular, classical dye inclusion or exclusion and colony formation assays. 20