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.
| Original language | English |
|---|---|
| Pages (from-to) | 629-633 |
| Number of pages | 5 |
| Journal | Cancer Chemotherapy and Pharmacology |
| Volume | 64 |
| Issue number | 3 |
| DOIs | |
| State | Published - Jul 2009 |
Bibliographical note
Funding Information: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 oYcial views of NIH. We thank Elisabeth Buchdunger (Novartis Pharmaceuticals, Basel, Switzerland) for providing STI571, and Leann Fiore for critically reading the manuscript.
Keywords
- Abl
- Cell Titer Glo (CTG)
- Gleevec
- MTT
- STI571
- Viability
ASJC Scopus subject areas
- Oncology
- Toxicology
- Pharmacology
- Cancer Research
- Pharmacology (medical)
