The combination of the tetrazolium derivative reduction (MTT) and digital cell image analysis to monitor in vitro the cytotoxicity of anti-neoplastic drugs.
We assessed the in vitro drug-induced cytotoxicity by means of the rapid low-cost but weakly sensitive Thiazolyl blue (MTT) test, and the less rapid, higher cost, but highly sensitive cell image analysis (CIA) test. We studied the influence of three drugs, i.e. a vinca-alkaloid (Navelbine), an alkylating investigational agent (PE1001), and an intercalating drug, i.e. adriamycin, on the proliferation (MTT test) and cell kinetics (CIA test) of the mouse MXT and the MCF-7 mammary cancer cell lines. Adriamycin and PE1001 decreased MXT and MCF-7 cell proliferation in a dose-dependent manner as assessed by both the MTT and CIA tests. Navelbine was highly cytotoxic in a dose-dependent manner. We demonstrated that Navelbine arrests cells in the M phase without altering the G2 phase. In sharp contrast, PE1001 arrest cells in the G2 phase without altering the M phase. An adriamycin-induced effect was apparent on S phase. Thus, the MTT test allows the screening of a great number of drugs analyzed at the cell proliferation level and, in the case of MTT positive drug-induced response, the CIA test enabled the drug-induced effect at cell cycle kinetic level to be investigated.
Etievant
C
C
Department de Pharmacologie Anti-cancereuse, Pierre Fabre Medicament, Castres, France.
Kruczynski
A
A
Pauwels
O
O
Kiss
R
R
D000230:Adenocarcinoma; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D004396:Coloring Agents; D004317:Doxorubicin / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D005260:Female; D006801:Humans; D007700:Kinetics; D051379:Mice; D010084:Oxidation-Reduction; D013778:Tetrazolium Salts; D013844:Thiazoles; D014747:Vinblastine / Q000031:analogs & derivatives / Q000494:pharmacology; D000077235:Vinorelbine
D000970:Antineoplastic Agents; D004396:Coloring Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; D014747:Vinblastine; D004317:Doxorubicin; C022616:thiazolyl blue; D000077235:Vinorelbine