A New Histone Deacetylase Inhibitor Enhances Radiation Sensitivity through the Induction of Misfolded Protein Aggregation and Autophagy in Triple-Negative Breast Cancer
Abstract
:1. Introduction
2. Results
2.1. Cytotoxic Effects of TMU-35435 and IR Treatment Separately or in Combination on TNBC Cells
2.2. Combination Treatment with TMU-35435 and IR Induces Misfolded Protein Aggregation, and TMU-35435 Inhibits the Interaction of HDAC6 with Dynein in 4T1 Cells
2.3. Measurement of Apoptosis and the Expression of ER Stress-Associated Proteins in Cells Treated with IR and TMU-35435 Separately or in Combination
2.4. Combined Treatment with IR and TMU-35435 Induces Autophagic Cell Death
2.5. Combination Treatment Inhibits Tumor Growth through the Induction of ER Stress and Autophagy in a Mouse Model of Orthotopic Breast Cancer
3. Discussion
4. Materials and Methods
4.1. Culture and Cell Viability Assay
4.2. Drug and IR Treatment
4.3. Drug Interaction Analysis
4.4. Clonogenic Assay
4.5. Misfolded Protein Detection
4.6. Autophagy and Apoptosis Detections
4.7. Western Blotting and Immunoprecipitation (IP)-Western Blotting
4.8. RNA Interference (RNAi)
4.9. Transmission Electron Microscopy
4.10. In Vivo Orthotopic Breast Cancer Model
4.11. Biochemistry Test
4.12. Immunohistochemical (IHC) Staining Analysis
4.13. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Item/Group | Normal | 4T1 Cells | |||
---|---|---|---|---|---|
Control | TMU-35435 | IR | TMU-35435 + IR | ||
GOT (U/L) | 170.20 ± 23.87 | 186.40 ± 26.90 | 153.20 ± 12.49 | 140.80 ± 10.84 | 158.20 ± 15.94 |
GPT (U/L) | 43.40 ± 4.06 | 33.00 ± 1.41 | 38.60 ± 3.78 | 34.80 ± 1.11 | 36.00 ± 1.38 |
Albumin (g/dL) | 1.80 ± 0.03 | 1.72 ±0.08 | 1.62 ± 0.07 | 1.78 ± 0.06 | 1.76 ± 0.07 |
BUN (mg/dL) | 24.52 ± 0.40 | 24.52 ± 1.26 | 22.92 ± 0.77 | 23.36 ± 1.41 | 22.82 ± 1.57 |
Creatinine (mg/dL) | 0.24 ± 0.02 | 0.26 ± 0.02 | 0.28 ± 0.02 | 0.26 ± 0.02 | 0.22 ± 0.02 |
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Chiu, H.-W.; Yeh, Y.-L.; Ho, S.-Y.; Wu, Y.-H.; Wang, B.-J.; Huang, W.-J.; Ho, Y.-S.; Wang, Y.-J.; Chen, L.-C.; Tu, S.-H. A New Histone Deacetylase Inhibitor Enhances Radiation Sensitivity through the Induction of Misfolded Protein Aggregation and Autophagy in Triple-Negative Breast Cancer. Cancers 2019, 11, 1703. https://0-doi-org.brum.beds.ac.uk/10.3390/cancers11111703
Chiu H-W, Yeh Y-L, Ho S-Y, Wu Y-H, Wang B-J, Huang W-J, Ho Y-S, Wang Y-J, Chen L-C, Tu S-H. A New Histone Deacetylase Inhibitor Enhances Radiation Sensitivity through the Induction of Misfolded Protein Aggregation and Autophagy in Triple-Negative Breast Cancer. Cancers. 2019; 11(11):1703. https://0-doi-org.brum.beds.ac.uk/10.3390/cancers11111703
Chicago/Turabian StyleChiu, Hui-Wen, Ya-Ling Yeh, Sheng-Yow Ho, Yuan-Hua Wu, Bour-Jr Wang, Wei-Jan Huang, Yuan-Soon Ho, Ying-Jan Wang, Li-Ching Chen, and Shih-Hsin Tu. 2019. "A New Histone Deacetylase Inhibitor Enhances Radiation Sensitivity through the Induction of Misfolded Protein Aggregation and Autophagy in Triple-Negative Breast Cancer" Cancers 11, no. 11: 1703. https://0-doi-org.brum.beds.ac.uk/10.3390/cancers11111703