The Gold(I) Complex with Plant Hormone Kinetin Shows Promising In Vitro Anticancer and PPARγ Properties
Abstract
:1. Introduction
2. Results and Discussion
2.1. General Characterization
2.2. Single Crystal X-ray Analysis
2.3. In Vitro Cytotoxicity Studies
2.4. Time-Dependent In Vitro Cytotoxicity and Cellular Uptake of Gold Complexes in A2780 Cells
2.5. Modification of A2780 Cell Cycle by the Gold(I) Complexes
2.6. Induction of Cell Death in A2780 Cells
2.7. The Effect of Gold(I) Complexes on Intracellular ROS Levels and Damage to the Mitochondrial Membranes
2.8. The Effect on NF-κB Activity Induced by LPS and PPARγ
2.9. Proteomic Analysis of Gold(I) Complexes [Au(kin)(PPh3)] (1) and [Au(PPh3)Cl] on Changes in the Proteome of R2780 Cells
3. Materials and Methods
3.1. General Methods Used for Characterization
3.2. Materials
3.3. Preparation and Characterization of the Complex (1)
3.4. Single-Crystal X-ray Diffraction Analysis
3.5. In Vitro Cytotoxicity against Human Cancerous and Normal Cell Lines
3.6. Cell Cycle Analysis
3.7. Induction of Cell Death and Related Processes
3.8. Induction of Autophagy
3.9. Induction of Intracellular ROS/Superoxide Production
3.10. Mitochondrial Membrane Potential Analysis
3.11. Cell Maintenance and Viability Determination
3.12. NF-κB Activity Determination
3.13. Immunocytochemical Analysis of PPARγ Expression and Localisation
3.14. Proteomic Analysis
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Compound | [Au(kin)(PPh3)] | [Au(L1)(PPh3)] a | [Au(L2)(PPh3)] b | |
---|---|---|---|---|
Selected bond lengths (Å) | Au-N(9) | 2.046(3) | 2.046(3) | 2.042(3) |
Au-P | 2.2379(10) | 2.2344(9) | 2.2356(8) | |
Selected angle (°) | N(9)-Au-P | 178.64(9) | 173.73(10) | 175.65(8) |
Compound | Human Cell Lines | ||||||
---|---|---|---|---|---|---|---|
A2780 | A2780R | PC-3 | 22Rv1 | THP-1 | LS180 | MRC5 | |
[Au(kin)(PPh3)] (1) | 2.9 ± 0.7 | 5.0 ± 1.5 | 4.8 ± 1.3 | 3.7 ± 0.5 | 1.1 ± 0.2 | >10 | >10 |
Kinetin | >25 | >25 | >25 | n.d. | n.d. | n.d. | >25 |
[Au(PPh3)Cl] | 3.5 ± 0.5 | 5.2 ± 0.2 | 9.9 ± 0.4 | n.d. | n.d. | n.d. | 17.0 ± 0.5 |
Auranofin | 3.4 ± 0.9 | 3.4 ± 0.6 | 3.7 ± 0.7 | n.d. | n.d. | n.d. | 3.78 ± 0.01 |
Cisplatin | 17.2 ± 0.9 | >50 | >50 | 28.2 ± 4.2 | n.d. | >50 | >50 |
Compound | 24 h | 48 h | 72 h |
---|---|---|---|
[Au(kin)(PPh3)] (1) | 2.9 ± 0.7 | 3.0 ± 0.3 | 3.0 ± 0.6 |
[Au(PPh3)Cl] | 3.5 ± 0.5 | 3.2 ± 0.2 | 3.1 ± 0.3 |
Auranofin | 3.4 ± 0.9 | 2.1 ± 0.4 | 2.0 ± 0.1 |
Cisplatin | 17.2 ± 0.9 | 12.4 ± 1.8 | 5.8 ± 1.8 |
Empirical formula Formula weight Temperature Wavelength Crystal system Space group Unit cell dimensions Volume Z Density (calculated) Absorption coefficient F(000) Crystal size θ range for data collection Index ranges Reflections collected Independent reflections Completeness to θ = 25.242° Absorption correction Refinement method Data/restraints/parameters Goodness-of-fit on F2 Final R indices [I > 2σ(I)] R indices (all data) Extinction coefficient | C28 H23 Au N5 O P 673.45 293(2) K 0.71073 Å Triclinic P-1 a = 10.050(4) Å, α = 88.980(12)° b = 11.779(5) Å, β = 79.919(15)° c = 13.847(5) Å, γ = 70.122(19)° 1516.2(10) Å3 2 1.475 g/cm3 4.930 mm−1 656 0.08 × 0.08 × 0.06 mm 1.84 to 27.59°. −13 ≤ h ≤ 13, −15≤ ≤ k ≤ 15, −17 ≤ l ≤17 41,317 6986 [R(int) = 0.0744] 100.0% Semi-empirical from equivalents Full-matrix least-squares on F2 6986/0/325 1.044 R1 = 0.0313, wR2 = 0.0546 R1 = 0.0539, wR2 = 0.0602 n/a |
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Trávníček, Z.; Vančo, J.; Belza, J.; Hošek, J.; Dvořák, Z.; Lenobel, R.; Popa, I.; Šmejkal, K.; Uhrin, P. The Gold(I) Complex with Plant Hormone Kinetin Shows Promising In Vitro Anticancer and PPARγ Properties. Int. J. Mol. Sci. 2023, 24, 2293. https://doi.org/10.3390/ijms24032293
Trávníček Z, Vančo J, Belza J, Hošek J, Dvořák Z, Lenobel R, Popa I, Šmejkal K, Uhrin P. The Gold(I) Complex with Plant Hormone Kinetin Shows Promising In Vitro Anticancer and PPARγ Properties. International Journal of Molecular Sciences. 2023; 24(3):2293. https://doi.org/10.3390/ijms24032293
Chicago/Turabian StyleTrávníček, Zdeněk, Ján Vančo, Jan Belza, Jan Hošek, Zdeněk Dvořák, René Lenobel, Igor Popa, Karel Šmejkal, and Pavel Uhrin. 2023. "The Gold(I) Complex with Plant Hormone Kinetin Shows Promising In Vitro Anticancer and PPARγ Properties" International Journal of Molecular Sciences 24, no. 3: 2293. https://doi.org/10.3390/ijms24032293
APA StyleTrávníček, Z., Vančo, J., Belza, J., Hošek, J., Dvořák, Z., Lenobel, R., Popa, I., Šmejkal, K., & Uhrin, P. (2023). The Gold(I) Complex with Plant Hormone Kinetin Shows Promising In Vitro Anticancer and PPARγ Properties. International Journal of Molecular Sciences, 24(3), 2293. https://doi.org/10.3390/ijms24032293