Anticancer Activity of the Acetylenic Derivative of Betulin Phosphate Involves Induction of Necrotic-Like Death in Breast Cancer Cells In Vitro
Abstract
:1. Introduction
2. Results
2.1. Synthesis of Betulin Derivatives (2–5)
2.2. Assessment of Cell Proliferation
2.3. Analysis of Cell Death
2.4. 30-diethoxyphosphoryl-28-propynoylbetulin Induces P21WAF1/Cip1 mRNA and Protein Expression
2.5. 30-diethoxyphosphoryl-28-propynoylbetulin Causes an Early Damage of Mitochondrial Function
2.6. 30-diethoxyphosphoryl-28-propynoylbetulin Increases Caspase-3 Activity
2.7. Intracellular Production of Reactive Oxidative Species
2.8. Morphological Analysis of Cells Treated with 30-diethoxyphosphoryl-28-propynoylbetulin
3. Discussion
4. Materials and Methods
4.1. Materials
Synthesis of 28-diethoxyphosphoryl-3-propynoylbetulin (5)
4.2. Cell Cultures
4.3. Sulforhodamine B (SRB) Assay
4.4. Determination of DNA Synthesis
4.5. Cytotoxicity Assays
4.6. DNA Fragmentation Assay
4.7. Gene and Protein Expression
4.8. Assessment of Mitochondrial Membrane Potential
4.9. Caspase-3 Activity Assay
4.10. Measurement of the Production of Reactive Oxygen Species
4.11. Acridine Orange Staining
4.12. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Sample Availability
References
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Compound | IC50 (µM) | |
---|---|---|
SK-BR-3 | MCF7 | |
1 | 7.93 ± 1.05 | 13.26 ± 0.75 |
2 | 3.83 ± 0.34 | n.d. |
3 | 2.89 ± 0.56 | n.d. |
4 | 2.12 ± 0.59 | 5.34 ± 0.03 |
5 | 3.49 ± 0.32 | 12.88 ± 0.96 |
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Orchel, A.; Chodurek, E.; Jaworska-Kik, M.; Paduszyński, P.; Kaps, A.; Chrobak, E.; Bębenek, E.; Boryczka, S.; Borkowska, P.; Kasperczyk, J. Anticancer Activity of the Acetylenic Derivative of Betulin Phosphate Involves Induction of Necrotic-Like Death in Breast Cancer Cells In Vitro. Molecules 2021, 26, 615. https://doi.org/10.3390/molecules26030615
Orchel A, Chodurek E, Jaworska-Kik M, Paduszyński P, Kaps A, Chrobak E, Bębenek E, Boryczka S, Borkowska P, Kasperczyk J. Anticancer Activity of the Acetylenic Derivative of Betulin Phosphate Involves Induction of Necrotic-Like Death in Breast Cancer Cells In Vitro. Molecules. 2021; 26(3):615. https://doi.org/10.3390/molecules26030615
Chicago/Turabian StyleOrchel, Arkadiusz, Ewa Chodurek, Marzena Jaworska-Kik, Piotr Paduszyński, Anna Kaps, Elwira Chrobak, Ewa Bębenek, Stanisław Boryczka, Paulina Borkowska, and Janusz Kasperczyk. 2021. "Anticancer Activity of the Acetylenic Derivative of Betulin Phosphate Involves Induction of Necrotic-Like Death in Breast Cancer Cells In Vitro" Molecules 26, no. 3: 615. https://doi.org/10.3390/molecules26030615