Screening of Phenanthroquinolizidine Alkaloid Derivatives for Inducing Cell Death of L1210 Leukemia Cells with Negative and Positive P-glycoprotein Expression
| Autor: | Katarína Elefantová, Boris Lakatoš, Petra Olejníková, Jana Kubíčková, Zdena Sulova, Martin Cagala, Peter Šafář, Albert Breier, Lucia Pavlikova, Kamila Ďurišová, Viera Bohacova, Mário Šereš, Štefan Marchalín |
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| Rok vydání: | 2019 |
| Předmět: |
Models
Molecular Necrosis Drug Evaluation Preclinical Pharmaceutical Science 01 natural sciences Analytical Chemistry Drug Discovery Cytotoxic T cell bcl-2-Associated X Protein P-glycoprotein 0303 health sciences Leukemia biology Caspase 3 Chemistry Cell Cycle apoptosis phenanthroquinolizidine alkaloids Cell cycle Chemistry (miscellaneous) Molecular Medicine medicine.symptom Quinolizines Phenanthrolines medicine.drug Vincristine Programmed cell death Article lcsh:QD241-441 Inhibitory Concentration 50 03 medical and health sciences lcsh:Organic chemistry multidrug resistance Cell Line Tumor medicine Humans ATP Binding Cassette Transporter Subfamily B Member 1 Physical and Theoretical Chemistry L1210 cells 030304 developmental biology Staining and Labeling 010405 organic chemistry Organic Chemistry Molecular biology 0104 chemical sciences Enzyme Activation Apoptosis biology.protein |
| Zdroj: | Molecules, Vol 24, Iss 11, p 2127 (2019) Molecules Volume 24 Issue 11 |
| ISSN: | 1420-3049 |
| Popis: | We describe the screening of a set of cryptopleurine derivatives, namely thienoquinolizidine derivatives and (epi-)benzo analogs with bioactive phenanthroquinolizidine alkaloids that induce cytotoxic effects in the mouse lymphocytic leukemia cell line L1210. We used three variants of L1210 cells: i) parental cells (S) negative for P-glycoprotein (P-gp) expression ii) P-glycoprotein positive cells (R), obtained by selection with vincristine iii) P-glycoprotein positive cells (T), obtained by stable transfection with a human gene encoding P-glycoprotein. We identified the most effective derivative 11 with a median lethal concentration of 13 &mu M in all three L1210 cell variants. The analysis of the apoptosis/necrosis induced by derivative 11 revealed that cell death was the result of apoptosis with late apoptosis characteristics. Derivative 11 did not induce a strong alteration in the proportion of cells in the G1, S or G2/M phase of the cell cycle, but a strong increase in the number of S, R and T cells in the subG1 phase was detected. These findings indicated that we identified the most effective inducer of cell death, derivative 11, and this derivative effectively induced cell death in S, R and T cells at similar inhibitory concentrations independent of P-gp expression. |
| Databáze: | OpenAIRE |
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