JNC-1043, a Novel Podophyllotoxin Derivative, Exerts Anticancer Drug and Radiosensitizer Effects in Colorectal Cancer Cells
Abstract
:1. Introduction
2. Results
2.1. JNC-1043 Inhibits Proliferation in CRC Cell Lines by Inducing DNA Damage
2.2. JNC-1043 Acts as a Radiosensitizer by Inhibiting Cell Growth In Vitro
2.3. Combination of JNC-1043 and IR Enhances Apoptosis and DNA Damage
2.4. The Combination of JNC-1043 and IR Induces Cell Cycle Arrest at G2/M Phase
2.5. Co-Treatment of JNC-1043 and IR Enhances the Accumulation of ROS in CRC Cells
2.6. ROS Is Important for the Radiosensitizing Effect of JNC-1043 against CRC Cells
2.7. In Vivo Radiosensitization Effect of JNC-1043
3. Discussion
4. Materials and Methods
4.1. Cell Culture and Chemical Reagents
4.2. MTT Assay and IC50 Determination
4.3. Clonogenic Assay
4.4. Cell Counting Assay
4.5. Cell Cycle Analysis
4.6. Immunoblot Analysis
4.7. Isolation of Mitochondrial and Cytosolic Fractions
4.8. Annexin V-Propidium Iodide Assay
4.9. Cellular ROS Detection Assay
4.10. Mitochondrial ROS Detection Assay
4.11. Mitochondrial Membrane Potential (ΔΨm) Detection Assay
4.12. TUNEL Assay
4.13. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Sample Availability
References
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IC50 Value (µM) | ||
---|---|---|
48 h | 72 h | |
HCT116 | 0.1719 | 0.1145 |
DLD-1 | 0.1598 | 0.1570 |
DER (Dose-Enhancement Ratio) | |
---|---|
110 or 150 nM | |
HCT116 | 1.53 |
DLD-1 | 1.25 |
HCT116 | Con | IR (1 Gy) | JNC-1043 | IR+JNC-1043 |
---|---|---|---|---|
Sub-G1 | 3.2 ± 0.3 | 1.7 ± 0.1 | 3.1 ± 0.3 | 3.5 ± 0.3 |
G1 | 38.5 ± 5.9 | 19.5 ± 3.4 | 22.2 ± 2.3 | 14.4 ± 2.0 |
S | 12.6 ± 0.9 | 13.3 ± 0.9 | 12.2 ± 1.9 | 15.8 ± 4.0 |
G2/M | 31.1± 2.1 | 40.5 ± 3.1 | 40.7 ± 0.6 | 50.7 ± 2.3 |
DLD-1 | Con | IR (1 Gy) | JNC-1043 | IR+JNC-1043 |
Sub-G1 | 1.4 ± 0.3 | 0.5 ± 0.3 | 1.1 ± 0.1 | 0.8 ± 0.1 |
G1 | 40.1 ± 4.0 | 34.7 ± 3.5 | 32.4 ± 5.0 | 30.4 ± 4.0 |
S | 13.4 ± 3.0 | 13.4 ± 1.9 | 15.7 ± 1.9 | 10.8 ± 1.5 |
G2/M | 25.9 ± 5.4 | 32.8 ± 5.0 | 33.8 ± 3.1 | 40 ± 5.0 |
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Kwon, J.-H.; Lee, N.-G.; Kang, A.-R.; Ahn, I.-H.; Choi, I.-Y.; Song, J.-Y.; Hwang, S.-G.; Um, H.-D.; Choi, J.-R.; Kim, J.; et al. JNC-1043, a Novel Podophyllotoxin Derivative, Exerts Anticancer Drug and Radiosensitizer Effects in Colorectal Cancer Cells. Molecules 2022, 27, 7008. https://doi.org/10.3390/molecules27207008
Kwon J-H, Lee N-G, Kang A-R, Ahn I-H, Choi I-Y, Song J-Y, Hwang S-G, Um H-D, Choi J-R, Kim J, et al. JNC-1043, a Novel Podophyllotoxin Derivative, Exerts Anticancer Drug and Radiosensitizer Effects in Colorectal Cancer Cells. Molecules. 2022; 27(20):7008. https://doi.org/10.3390/molecules27207008
Chicago/Turabian StyleKwon, Jin-Hee, Na-Gyeong Lee, A-Ram Kang, In-Ho Ahn, In-Young Choi, Jie-Young Song, Sang-Gu Hwang, Hong-Duck Um, Jong-Ryoo Choi, Joon Kim, and et al. 2022. "JNC-1043, a Novel Podophyllotoxin Derivative, Exerts Anticancer Drug and Radiosensitizer Effects in Colorectal Cancer Cells" Molecules 27, no. 20: 7008. https://doi.org/10.3390/molecules27207008