A Novel ALDH1A1 Inhibitor Blocks Platinum-Induced Senescence and Stemness in Ovarian Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Chemical Reagents
2.2. Protein Purification and Enzymatic Assays
2.3. X-ray Crystallography
2.4. Cell Culture
2.5. Flow Cytometry
2.6. Quantitative PCR
2.7. Senescence Beta (β)-Gal Assay
2.8. RNA Sequencing and Bioinformatic Analysis
2.9. Mouse Xenograft Experiment
2.10. Colony Formation and Tumorsphere Assay
2.11. MTT Cell Proliferation Assay
2.12. Cell Transfection and Plasmids
2.13. Western Blotting
2.14. Statistical Analysis
2.15. Data Availability
3. Results
3.1. Discovery of 974, a Novel ALDH1A1-Specific Small-Molecule Inhibitor
3.2. ALDH1A1 Inhibition Suppresses Stemness Phenotypes in Ovarian Cancer Cells
3.3. ALDH1A1 Inhibition Suppresses Ovarian Cancer Stemness In Vivo
3.4. ALDH1A1 Inhibition Downregulates Key Stemness and Chemoresistance Pathways
3.5. Inhibition of ALDH1A1 Suppresses Chemotherapy-Induced Senescence and Stemness
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Muralikrishnan, V.; Fang, F.; Given, T.C.; Podicheti, R.; Chtcherbinine, M.; Metcalfe, T.X.; Sriramkumar, S.; O’Hagan, H.M.; Hurley, T.D.; Nephew, K.P. A Novel ALDH1A1 Inhibitor Blocks Platinum-Induced Senescence and Stemness in Ovarian Cancer. Cancers 2022, 14, 3437. https://doi.org/10.3390/cancers14143437
Muralikrishnan V, Fang F, Given TC, Podicheti R, Chtcherbinine M, Metcalfe TX, Sriramkumar S, O’Hagan HM, Hurley TD, Nephew KP. A Novel ALDH1A1 Inhibitor Blocks Platinum-Induced Senescence and Stemness in Ovarian Cancer. Cancers. 2022; 14(14):3437. https://doi.org/10.3390/cancers14143437
Chicago/Turabian StyleMuralikrishnan, Vaishnavi, Fang Fang, Tyler C. Given, Ram Podicheti, Mikhail Chtcherbinine, Tara X. Metcalfe, Shruthi Sriramkumar, Heather M. O’Hagan, Thomas D. Hurley, and Kenneth P. Nephew. 2022. "A Novel ALDH1A1 Inhibitor Blocks Platinum-Induced Senescence and Stemness in Ovarian Cancer" Cancers 14, no. 14: 3437. https://doi.org/10.3390/cancers14143437