Abstract
Purpose
This study will determine whether MTT assays accurately assess the effect of STI571 (Gleevec; Abl kinase inhibitor) on the viability of cancer cells containing highly active Abl kinases.
Methods
Growth kinetics, tritiated thymidine, fluorescent caspase, MTT, and Cell Titer Glo (CTG) assays were used to determine the effect of STI571 on growth, proliferation, apoptosis, and viability of melanoma and breast cancer cells.
Results
STI571 inhibited growth and proliferation, and increased apoptosis. However, MTT assays indicated that STI571 increased cell viability. In contrast, STI571 induced a dose-dependent decrease in viability using CTG assays.
Conclusions
Doses of STI571 (1–10 μM) required to inhibit endogenous Abl kinases interfere with the MTT assay, and therefore MTT cannot be used to determine the effect of STI571 on viability using these doses. Additionally, caution should be utilized when interpreting the results of MTT assays used to screen kinase inhibitors for anti-cancer activity, as drug effectiveness may be minimized.
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Acknowledgments
This work was supported by National Institute of Health Grant P20 RR20171 from the National Center for Research Resources, and National Institute of Health/National Cancer Institute Grant 1R01CA116784 to R.P. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of NIH. We thank Elisabeth Buchdunger (Novartis Pharmaceuticals, Basel, Switzerland) for providing STI571, and Leann Fiore for critically reading the manuscript.
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Sims, J.T., Plattner, R. MTT assays cannot be utilized to study the effects of STI571/Gleevec on the viability of solid tumor cell lines. Cancer Chemother Pharmacol 64, 629–633 (2009). https://doi.org/10.1007/s00280-009-1004-y
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DOI: https://doi.org/10.1007/s00280-009-1004-y