AKF-D52, a Synthetic Phenoxypyrimidine-Urea Derivative, Triggers Extrinsic/Intrinsic Apoptosis and Cytoprotective Autophagy in Human Non-Small Cell Lung Cancer Cells
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Reagents and Chemicals
2.2. Cell Culture
2.3. MTT Assay
2.4. DAPI Staining
2.5. Annexin V/PI Staining for Apoptosis Analysis
2.6. Nuclear Extraction
2.7. Western Blot Analysis
2.8. Analysis of Mitochondrial Membrane Potential (ΔΨm)
2.9. Preparation of Cytosolic and Mitochondrial Fractionation
2.10. Immunoprecipitation Assay
2.11. Acridine Orange Staining
2.12. Measurement of Reactive Oxygen Species (ROS)
2.13. Animals
2.14. In Vivo Tumor Xenograft Studies
2.15. Measurement of Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Blood Urea Nitrogen (BUN) Levels
2.16. Statistical Analysis
3. Results
3.1. AKF-D52 Suppresses Cell Viability via Apoptotic Cell Death in A549 and NCI-H358 Cells
3.2. AKF-D52 Concurrently Induces Caspase-Dependent and -Independent Apoptosis in A549 and NCI-H358 Cells
3.3. AKF-D52-Induced Apoptosis Is Dependent on Mitochondrial Dysfunction in A549 and NCI-H358 Cells
3.4. AKF-D52-Induced Apoptosis Requires Death-Inducing Signaling Complex Activation in A549 and NCI-H358 Cells
3.5. Inhibition of Cytoprotective Autophagy Enhances AKF-D52-Induced Apoptosis in A549 and NCI-H358 Cells
3.6. ROS Plays an Important Role in AKF-D52-Induced Apoptosis in A549 and NCI-H358 Cells
3.7. AKF-D52 Inhibits Tumor Growth in an A549 Xenograft Mouse Model
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Gil, H.-S.; Lee, J.-H.; Farag, A.K.; Hassan, A.H.E.; Chung, K.-S.; Choi, J.-H.; Roh, E.-J.; Lee, K.-T. AKF-D52, a Synthetic Phenoxypyrimidine-Urea Derivative, Triggers Extrinsic/Intrinsic Apoptosis and Cytoprotective Autophagy in Human Non-Small Cell Lung Cancer Cells. Cancers 2021, 13, 5849. https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13225849
Gil H-S, Lee J-H, Farag AK, Hassan AHE, Chung K-S, Choi J-H, Roh E-J, Lee K-T. AKF-D52, a Synthetic Phenoxypyrimidine-Urea Derivative, Triggers Extrinsic/Intrinsic Apoptosis and Cytoprotective Autophagy in Human Non-Small Cell Lung Cancer Cells. Cancers. 2021; 13(22):5849. https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13225849
Chicago/Turabian StyleGil, Hyo-Sun, Jeong-Hun Lee, Ahmed K. Farag, Ahmed H. E. Hassan, Kyung-Sook Chung, Jung-Hye Choi, Eun-Joo Roh, and Kyung-Tae Lee. 2021. "AKF-D52, a Synthetic Phenoxypyrimidine-Urea Derivative, Triggers Extrinsic/Intrinsic Apoptosis and Cytoprotective Autophagy in Human Non-Small Cell Lung Cancer Cells" Cancers 13, no. 22: 5849. https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13225849