MTT assays cannot be utilized to study the effects of STI571/Gleevec on the viability of solid tumor cell lines

• Published in: Cancer chemotherapy and pharmacology 2009-07, Vol.64 (3), p.629-633
• Main Authors: Sims, Jonathan T, Plattner, Rina
• Format: Article
• Language: English
• Subjects: Antineoplastic agents; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Benzamides; Biological and medical sciences; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Cancer Research; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor - methods; Fusion Proteins, bcr-abl; Humans; Imatinib Mesylate; Medical sciences; Medicine; Medicine & Public Health; Melanoma - drug therapy; Melanoma - pathology; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Oncology; Pharmacology. Drug treatments; Pharmacology/Toxicology; Piperazines - administration & dosage; Piperazines - pharmacology; Protein-Tyrosine Kinases - antagonists & inhibitors; Pyrimidines - administration & dosage; Pyrimidines - pharmacology; Short Communication; Tetrazolium Salts; Thiazoles; Tumors
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/s00280-009-1004-y

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.