Evaluation of the time-schedule dependency for the cytotoxic activity of the new vinca alkaloid derivative, S 12363 (Vinfosiltine)
| Autor: | Jean-Louis Fischel, M. Berlion, J. P. Bizzari, Patricia Formento, Gérard Milano |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
Cancer Research
Time Factors Cell Survival medicine.drug_class Pharmacology Vinca alkaloid Toxicology chemistry.chemical_compound Tumor Cells Cultured medicine Humans Cytotoxic T cell Cytotoxicity Vinca Alkaloids Dose-Response Relationship Drug business.industry Vinfosiltine Antineoplastic Agents Phytogenic In vitro Vinblastine Oncology chemistry Cell culture Drug Screening Assays Antitumor Growth inhibition business medicine.drug |
| Zdroj: | European Journal of Cancer. 29:1890-1894 |
| ISSN: | 0959-8049 |
| DOI: | 10.1016/0959-8049(93)90544-p |
| Popis: | S 12363 is a new vinca alkaloid derivative obtained by appending an optically active α-aminophosphonate at the C23 position of 04-deacetyl vinblastine. The present study concerns four different human tumour cell lines, which represent the spectrum of vinca alkaloid clinical activity. The influence of time exposure on S 12363 growth inhibition was studied in vitro . Cells were exposed to the drug during the following exposure times: 5, 15, 30 min and 1, 3, 6, 12, 24, 48, 72, 144 h. The concentrations of S 12363 applied were between 1 × 10 −2 and 1 × 10 3 nmol/l. The cytotoxic effects were assessed by using the methyltetrazolium (MTT) semi-automated test. Considering the ic 50 values in terms of concentration (C) × time (T), i (C × T) 50 , it was shown that for an equal growth inhibitory effect (50% of cell death) the increased exposure times required higher cumulative drug exposures. More precisely, only very long exposure (greater than 24 h) resulted in very high i (C × T) 50 . The drug exposure ratios which correspond to i (C × T) 50 values for 144 h divided by the i (C × T) 50 values for 0.25 h ranged between 2.8 and 18.3. If T and C had symmetrical effects on the final growth inhibition, the i (C × T) 50 ratios should have been equal to one. For all cell lines investigated there were similar dose-response curves following two types of S12363 exposure: a single day exposure or three successive daily exposures, the total C × T values being the same in both experimental situations. The basic pharmacological information provided by the present study may encourage further clinical trials of this potentially interesting new vinca alkaloid. |
| Databáze: | OpenAIRE |
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