Dissecting the Anticancer Mechanism of Trifluoperazine on Pancreatic Ductal Adenocarcinoma
Abstract
:1. Introduction
2. Results
2.1. Trifluoperazine Induces Both Necrosis and Apoptosis in Pancreatic Cancer Cells
2.2. Trifluoperazine Decreases the Intracellular ATP Production
2.3. Trifluoperazine-treatment Induces Mitochondrial and Endoplasmic Coupled Stress
2.4. Proteasome System Activity was Activated after Trifluoperazine-treatment
2.5. Proteasome Inhibition Increases Sensitivity to Trifluoperazine of Primary Pancreatic Cancer Cells
3. Discussion
4. Materials and Methods
4.1. Cell Culture
4.2. LDH Assay, ATP Production, and Caspase-3/7 Activity Assay
4.3. qRT-PCR
4.4. Western Blot Analysis
4.5. Extracellular Flux Assay
4.6. Lactate Release, Glucose and Glutamine Uptake
4.7. Annexin V/PI Staining
4.8. ROS Measurements
4.9. Mitochondrial Membrane Potential
4.10. Cytosolic Calcium Concentration
4.11. Mitochondrial Network
4.12. Electron Microscopy
4.13. Chemograms and Viability Assays
4.14. Proteasome Activity Assay
4.15. Statistics
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Cell Line | IC50 (µM) | AUC (a.u.) | ||||
---|---|---|---|---|---|---|
TFP | TFP + MG-132 | TFP + bortezomib | TFP | TFP + MG-132 | TFP + bortezomib | |
MiaPaCa-2 | 13.24 ± 0.21 | 5.46 ± 0.17 **** | 6.81 ± 0.20 **** | 1372.67 ± 101.18 | 618.13 ± 49.26 **** | 939.37 ± 19.02 **** |
1008 | 10.46 ± 0.48 | 8.05 ± 0.10 ** | 8,65 ± 0.11 * | 1507.67 ± 49.97 | 1260.00 ± 10.78 ** | 1140.67 ± 15.16 ** |
HN01 | 14.78 ± 0.044 | 2.47 ± 0.36 **** | 3.16 ± 0.29 **** | 1345.67 ± 15.026 | 525.7 ± 9.05 **** | 709.37 ± 24.60 **** |
JIPC | 11.45 ± 0.067 | 0.86 ± 0,01 **** | 2.02 ± 0.44 **** | 1218 ± 14.98 | 242.5 ± 1.84 **** | 425.43 ± 34.75 **** |
LIPC | 15.07 ± 8.07 | 5.81 ± 0.08 **** | 8.15 ± 0.09 **** | 1559 ± 28.583 | 754.1 ± 9.15 **** | 917 ± 16.49 **** |
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Share and Cite
Huang, C.; Lan, W.; Fraunhoffer, N.; Meilerman, A.; Iovanna, J.; Santofimia-Castaño, P. Dissecting the Anticancer Mechanism of Trifluoperazine on Pancreatic Ductal Adenocarcinoma. Cancers 2019, 11, 1869. https://doi.org/10.3390/cancers11121869
Huang C, Lan W, Fraunhoffer N, Meilerman A, Iovanna J, Santofimia-Castaño P. Dissecting the Anticancer Mechanism of Trifluoperazine on Pancreatic Ductal Adenocarcinoma. Cancers. 2019; 11(12):1869. https://doi.org/10.3390/cancers11121869
Chicago/Turabian StyleHuang, Can, Wenjun Lan, Nicolas Fraunhoffer, Analía Meilerman, Juan Iovanna, and Patricia Santofimia-Castaño. 2019. "Dissecting the Anticancer Mechanism of Trifluoperazine on Pancreatic Ductal Adenocarcinoma" Cancers 11, no. 12: 1869. https://doi.org/10.3390/cancers11121869