Cytotoxic Activity of Novel GnRH Analogs Conjugated with Mitoxantrone in Ovarian Cancer Cells
Abstract
:1. Introduction
2. Results
2.1. Con-3 and Con-7 Are GnRH-R Agonists
2.2. Con-3 and Con-7 Decrease the Proliferation of SKOV-3 Cells
2.3. Con-3 and Con-7 Induce Apoptosis in SKOV-3 Cells
2.4. Intracellular Accumulation of Mitoxantrone after Treatment of SKOV-3 Cells with Con-3 or Con-7
2.5. Cisplatin Inhibits the Intracellular Accumulation of Mitoxantrone of Con-3 and Con-7
3. Discussion
4. Materials and Methods
4.1. Calcium-Based Kinetic Assays of GnRH-R Agonism
4.2. Cell Proliferation Assays
4.3. Cell Apoptosis Assays
4.3.1. Annexin V Assay
4.3.2. TMRE-Based Detection of Mitochondrial Membrane Potential
4.4. Confocal Microscopy
4.5. Quantification of the Fluorescence Intensity
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Apoptotic Cells (%) | Control | Con-3 | Con-7 | Mitoxantrone | ||||
---|---|---|---|---|---|---|---|---|
Mean | SEM | Mean | SEM | Mean | SEM | Mean | SEM | |
Day2 | 2.12 | 0.67 | 13.68 * | 1.87 | 13.81 * | 1.58 | 14.26 * | 0.62 |
Day3 | 1.96 | 0.35 | 35.00 * | 3.50 | 33.53 * | 5.91 | 33.60 * | 3.00 |
Day4 | 3.69 | 0.70 | 49.50 * | 2.04 | 51.17 * | 4.22 | 50.10 * | 2.15 |
Fluorescence Intensity | SEM | |
---|---|---|
Con-7 | 9738 | 398.4 |
Con-7 + cisplatin | 3244 | 236.7 |
Con-3 | 9015 | 243.6 |
Con-3 + cisplatin | 2978 | 161.7 |
Mitoxantrone | 9078 | 396.1 |
Mitoxantrone + cisplatin | 9021 | 16.2 |
Control | 583 | 23.1 |
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Markatos, C.; Biniari, G.; Chepurny, O.G.; Karageorgos, V.; Tsakalakis, N.; Komontachakis, G.; Vlata, Z.; Venihaki, M.; Holz, G.G.; Tselios, T.; et al. Cytotoxic Activity of Novel GnRH Analogs Conjugated with Mitoxantrone in Ovarian Cancer Cells. Molecules 2024, 29, 4127. https://doi.org/10.3390/molecules29174127
Markatos C, Biniari G, Chepurny OG, Karageorgos V, Tsakalakis N, Komontachakis G, Vlata Z, Venihaki M, Holz GG, Tselios T, et al. Cytotoxic Activity of Novel GnRH Analogs Conjugated with Mitoxantrone in Ovarian Cancer Cells. Molecules. 2024; 29(17):4127. https://doi.org/10.3390/molecules29174127
Chicago/Turabian StyleMarkatos, Christos, Georgia Biniari, Oleg G. Chepurny, Vlasios Karageorgos, Nikos Tsakalakis, Georgios Komontachakis, Zacharenia Vlata, Maria Venihaki, George G. Holz, Theodore Tselios, and et al. 2024. "Cytotoxic Activity of Novel GnRH Analogs Conjugated with Mitoxantrone in Ovarian Cancer Cells" Molecules 29, no. 17: 4127. https://doi.org/10.3390/molecules29174127