Induction of Endoplasmic Reticulum Stress-Mediated Apoptosis by Aminosteroid RM-581 Efficiently Blocks the Growth of PC-3 Cancer Cells and Tumors Resistant or Not to Docetaxel
Abstract
:1. Introduction
2. Results
2.1. RM-581 and RM-581-Fluo Antiproliferative Activities
2.2. RM-581-Fluo Accumulates in ER of PC-3 Cells
2.3. RM-581 Induces ER-Stress and Apoptosis
2.4. RM-581 Impairs Lipid Homeostasis
2.5. RM-581 Blocks the Growth of PC-3 Cells and Docetaxel-Resistant PC-3 Cells
2.6. RM-581 Blocks Tumor Growth in PC-3 Xenografts
3. Discussion
4. Materials and Methods
4.1. Chemical Synthesis
4.2. Cell Culture
4.3. IC50 Determination of RM-581 vs. RM-581-Fluo in PC-3 Cells
4.4. Confocal Imaging of PC-3 Cells
4.5. Gene Expression Study (Real-Time PCR Analysis)
4.6. Apoptosis Characterization by Flow Cytometry
4.7. Cell Viability Proliferation Assays and Combination Index with Docetaxel
4.8. Induction of Docetaxel-Resistant PC-3 Cells
4.9. Effect of RM-581 in PC-3 Xenografts
4.10. Dosage of RM-581 in Tumors and Plasma of Treated Mice
4.11. Fatty Acid Determination in PC-3 Tumors
4.12. Statistical Analysis
5. 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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RM-581 Tumor (ng/g) | RM-581 Plasma (ng/mL) | Concentration Index * Tumor/Plasma |
---|---|---|
150 ± 71 | 50.5 ± 6.3 | 3.0 |
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Maltais, R.; Roy, J.; Perreault, M.; Sato, S.; Lévesque, J.-C.; Poirier, D. Induction of Endoplasmic Reticulum Stress-Mediated Apoptosis by Aminosteroid RM-581 Efficiently Blocks the Growth of PC-3 Cancer Cells and Tumors Resistant or Not to Docetaxel. Int. J. Mol. Sci. 2021, 22, 11181. https://doi.org/10.3390/ijms222011181
Maltais R, Roy J, Perreault M, Sato S, Lévesque J-C, Poirier D. Induction of Endoplasmic Reticulum Stress-Mediated Apoptosis by Aminosteroid RM-581 Efficiently Blocks the Growth of PC-3 Cancer Cells and Tumors Resistant or Not to Docetaxel. International Journal of Molecular Sciences. 2021; 22(20):11181. https://doi.org/10.3390/ijms222011181
Chicago/Turabian StyleMaltais, René, Jenny Roy, Martin Perreault, Sachiko Sato, Julie-Christine Lévesque, and Donald Poirier. 2021. "Induction of Endoplasmic Reticulum Stress-Mediated Apoptosis by Aminosteroid RM-581 Efficiently Blocks the Growth of PC-3 Cancer Cells and Tumors Resistant or Not to Docetaxel" International Journal of Molecular Sciences 22, no. 20: 11181. https://doi.org/10.3390/ijms222011181
APA StyleMaltais, R., Roy, J., Perreault, M., Sato, S., Lévesque, J.-C., & Poirier, D. (2021). Induction of Endoplasmic Reticulum Stress-Mediated Apoptosis by Aminosteroid RM-581 Efficiently Blocks the Growth of PC-3 Cancer Cells and Tumors Resistant or Not to Docetaxel. International Journal of Molecular Sciences, 22(20), 11181. https://doi.org/10.3390/ijms222011181