Triorganotin Derivatives Induce Cell Death Effects on L1210 Leukemia Cells at Submicromolar Concentrations Independently of P-glycoprotein Expression
Abstract
:1. Introduction
2. Results
2.1. Characterization of P-gp Positive Variants of L1210 Cells
2.2. Cytotoxic Effect of TBT and TPT Derivatives on S, R, T and PB-1 Cells
2.3. Effect of Triorganotin Derivatives on Expression and Drug Efflux Activity of P-gp
2.4. Mechanism of Triorganotin Cell Death Effects
2.5. Relations between the Effectiveness of the Cell Death Effects and Lipophilicity of Triorganotins
3. Discussion
4. Materials and Methods
4.1. Chemicals
4.2. Cell Culture Conditions
4.3. Cell Death Effects of Triorganotin Derivatives on S, R, T and PB-1 Cells
4.4. Reverse Transcription Polymerase Chain Reaction (RT-PCR) Detection of P-gp Expression
4.5. Estimation of P-gp Transport Activity by Calcein/AM Retention Assay
4.6. Measurement of S, R and T Cells’ Proportions in Apoptosis and Necrosis Using
4.7. Western Blot Procedures
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Sample Availability: Samples of the compounds TBT-NCS and TPT-NCS are available from the authors. |
Compound | Abbreviation | Structure 1 | Log P 2 |
---|---|---|---|
Tributyltin chloride (Chlorotributyltin, Chlorotributylstannane) | TBT-Cl | 3.46 | |
Tributyltin bromide (Bromotributyltin, Bromotributylstannane) | TBT-Br | 3.59 | |
Tributyltin iodide (Iodotributyltin, Iodotributylstannane) | TBT-I | 3.86 | |
Tributyltin isothiocyanate (Isothiocyanatotributyltin, Isothiocyanatotributylstannane) | TBT-NCS | 4.15 | |
Triphenyltin chloride (Chlorotriphenyltin, Chlorotriphenylstannane) | TPT-Cl | 4.24 | |
Triphenyltin isothiocyanate (Isothiocyanatotriphenyltin, Isothiocyanatotriphenylstannane) | TPT-NCS | 4.92 |
IC50 for | S | R | Rv | T | Tv |
---|---|---|---|---|---|
Substances | (in μM) | ||||
TBT-Cl | 0.29 ± 0.03 | 0.25 ± 0.02 * | 0.23 ± 0.05 * | 0.21 ± 0.05 ** | 0.21 ± 0.04 ** |
TBT-Br | 0.29 ± 0.05 | 0.15 ± 0.05 ** | 0.15 ± 0.04 ** | 0.17 ± 0.07 ** | 0.16 ± 0.04 ** |
TBT-I | 0.14 ± 0.02 | 0.18 ± 0.03 * | 0.15 ± 0.02 + | 0.21 ± 0.04 ** | 0.16 ± 0.03 + |
TPT-Cl | 0.37 ± 0.09 | 0.45 ± 0.09 | 0.44 ± 0.10 | 0.47 ± 0.11 | 0.48 ± 0.12 |
TBT-NCS | 0.31 ± 0.09 | 0.30 ± 0.05 | 0.33 ± 0.07 | 0.20 ± 0.05 * | 0.20 ± 0. 04 * |
TPT-NCS | 0.09 ± 0.02 | 0.24 ± 0.04 ** | 0.10 ± 0.02 ++ | 0.24 ± 0.06 ** | 0.09 ± 0.03 ++ |
Correlation | B0 | B1 | r | p | Significance |
---|---|---|---|---|---|
S vs. R | - | - | 0.582 | 0.226 | Insignificant |
S vs. T | - | - | 0.425 | 0.401 | Insignificant |
R vs. T | 0.008 | 0.928 (42,9°) | 0.902 | 0.014 | significant (p < 0.02) |
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Bohacova, V.; Seres, M.; Pavlikova, L.; Kontar, S.; Cagala, M.; Bobal, P.; Otevrel, J.; Brtko, J.; Sulova, Z.; Breier, A. Triorganotin Derivatives Induce Cell Death Effects on L1210 Leukemia Cells at Submicromolar Concentrations Independently of P-glycoprotein Expression. Molecules 2018, 23, 1053. https://doi.org/10.3390/molecules23051053
Bohacova V, Seres M, Pavlikova L, Kontar S, Cagala M, Bobal P, Otevrel J, Brtko J, Sulova Z, Breier A. Triorganotin Derivatives Induce Cell Death Effects on L1210 Leukemia Cells at Submicromolar Concentrations Independently of P-glycoprotein Expression. Molecules. 2018; 23(5):1053. https://doi.org/10.3390/molecules23051053
Chicago/Turabian StyleBohacova, Viera, Mario Seres, Lucia Pavlikova, Szilvia Kontar, Martin Cagala, Pavel Bobal, Jan Otevrel, Julius Brtko, Zdena Sulova, and Albert Breier. 2018. "Triorganotin Derivatives Induce Cell Death Effects on L1210 Leukemia Cells at Submicromolar Concentrations Independently of P-glycoprotein Expression" Molecules 23, no. 5: 1053. https://doi.org/10.3390/molecules23051053