Starvation Fools the Standard Cancer Cell Assay (MTT)
Since its introduction by TimMossman in 1983, the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay has been used to determine cell viability. MTT is quick, practical, and avoids radiation (unlike radio-labeled thymidine uptake). Many researchers use MTT to indicate the number cells that survive exposure to cancer drugs. This study shows why that is a bad idea under many experimental conditions.
MTT conversion is a marker of cellular metabolism, especially in the mitochondria where it is reduced by the enzyme succinate dehydrogenase (SDH). Although it is not a marker of cell death, MTT is often used to indicate cell killing in cancer studies.
Preliminary results show that MTT signal is not proportional to cell number under many experimental conditions, especially those that affect glucose availability. We were able to induce a hibernation-like phenomenon in mitochondrial function after 4 days of glucose starvation. This hibernation could easily be misinterpreted as cell death in studies that rely on MTT to determine viability and cell number. These cells were not dead, just resting.
Neumann, Chase, "Starvation Fools the Standard Cancer Cell Assay (MTT)" (2014). College of Arts and Sciences Presentations. 20.