Anticancer Activity and Molecular Mechanisms of an Ursodeoxycholic Acid Methyl Ester-Dihydroartemisinin Hybrid via a Triazole Linkage in Hepatocellular Carcinoma Cells
Abstract
:1. Introduction
2. Results
2.1. The Anticancer Effect of UDCMe-Z-DHA Is More Potent Than DHA in HCC Cells
2.2. UDCMe-Z-DHA Is More Stable Than DHA
2.3. The Effect of DHA and UDCMe-Z-DHA on Cell Cycle Progression and Apoptosis in HCC Cells
2.4. The Effect of DHA and UDCMe-Z-DHA on ROS Production in HepG2 Cells
2.5. The Effect of DHA and UDCMe-Z-DHA on Depolarization of MMP in HCC Cells
2.6. The Effect of DHA and UDCMe-Z-DHA on the MAPK Signaling Pathway in HepG2 Cells
2.7. The Effect of DHA and UDCMe-Z-DHA on the AMPK/Autophagy Signaling Pathway in HepG2 Cells
2.8. Autophagy Induced by UDCMe-Z-DHA May Be Associated with Apoptosis in HepG2 Cells
2.9. ROS Induced by UDCMe-Z-DHA May Cause Autophagy in HepG2 Cells
3. Discussion
4. Materials and Methods
4.1. Materials
4.2. Cell Lines and Cell Culture
4.3. Cell Viability Assay
4.4. HPLC-MS/MS Analysis
4.5. Cell Cycle Analysis
4.6. Western Blot Analysis
4.7. DCFH-DA Assay
4.8. JC-1 Assay
4.9. Data Analysis
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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Compound | HepG2 | Huh-7 | ||
---|---|---|---|---|
IC50 (μM) 1 | Ratio 2 | IC50 (μM) 1 | Ratio 2 | |
DHA | 22.7 ± 0.39 | 40.0 ± 1.34 | ||
UDCMe-Z-DHA | 1.00 ± 0.20 | 22.7 | 10.6 ± 2.28 | 3.77 |
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Hsu, Y.-F.; Kung, F.-L.; Huang, T.-E.; Deng, Y.-N.; Guh, J.-H.; Marchetti, P.; Marchesi, E.; Perrone, D.; Navacchia, M.L.; Hsu, L.-C. Anticancer Activity and Molecular Mechanisms of an Ursodeoxycholic Acid Methyl Ester-Dihydroartemisinin Hybrid via a Triazole Linkage in Hepatocellular Carcinoma Cells. Molecules 2023, 28, 2358. https://doi.org/10.3390/molecules28052358
Hsu Y-F, Kung F-L, Huang T-E, Deng Y-N, Guh J-H, Marchetti P, Marchesi E, Perrone D, Navacchia ML, Hsu L-C. Anticancer Activity and Molecular Mechanisms of an Ursodeoxycholic Acid Methyl Ester-Dihydroartemisinin Hybrid via a Triazole Linkage in Hepatocellular Carcinoma Cells. Molecules. 2023; 28(5):2358. https://doi.org/10.3390/molecules28052358
Chicago/Turabian StyleHsu, Ya-Fen, Fan-Lu Kung, Tzu-En Huang, Yi-Ning Deng, Jih-Hwa Guh, Paolo Marchetti, Elena Marchesi, Daniela Perrone, Maria Luisa Navacchia, and Lih-Ching Hsu. 2023. "Anticancer Activity and Molecular Mechanisms of an Ursodeoxycholic Acid Methyl Ester-Dihydroartemisinin Hybrid via a Triazole Linkage in Hepatocellular Carcinoma Cells" Molecules 28, no. 5: 2358. https://doi.org/10.3390/molecules28052358