Concurrent Activation of Both Survival-Promoting and Death-Inducing Signaling by Chloroquine in Glioblastoma Stem Cells: Implications for Potential Risks and Benefits of Using Chloroquine as Radiosensitizer
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cells and Cell-Based Assays
2.2. Cell Treatments and Cell-Based Assays
2.3. Animal Experiments
2.4. Protein Analyses
2.5. Gene Expression and Bioinformatics
2.6. Statistical Analysis
3. Results
3.1. Impact of ClQ Alone or in Combination with IR on GSCs Proliferation and Viability In Vitro
3.2. In Vivo Effects of ClQ Alone or in Combination with IR on the Tumor-Propagating Capacity of GSCs
3.3. ClQ Elicits Distinct Molecular Outcomes in GSCs Differing for the Status of p53
3.4. ClQ Induces Transcriptional Repression via the p53-p21-DREAM Pathway Concurrently with Transcriptional Activation of the Mevalonate Pathway
3.5. Impacts of ClQ on the Apoptotic Signaling
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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ClQ_DEGs_#993 (wtp53) | ||
---|---|---|
p53RGs (80) * p21-DREAM | down-regulated anln *; arhgap11a *; arhgap11b *; aspm *; aurka *; bub1 *; bub1b *; casc5 *; c11orf82 *; c12orf48 *; ccdc18 *; ccna2 *; ccnb1 *; ccnb2 *; ccne2; cdc2; cdca2 *; cdca3 *; cdca8 *; cdc25c *; cdkn3 *; cenpe *; cit *; ckap2l *; dc; depdc1 *; depdc1b *; dlgap5 *; esco2 *; exo1 *, fam64a *; fancb *; fancd2 **; fanci **; gas2l3 *; gtse1 *; hist1h2bm *; hjurp *; hmmr *; kif2c *; kif4a *; kif11 *; kif14 *; kif15 *; kif18a *; kif20a *; kif20b *; kif23 *; kif24 *; mad2l1 *; melk *; mki67 *; ncapg *; ncapg2 *; ncaph *; ndc80 *; neil3 *; nuf2 *; nusap1 *; plk1 *; plk4 *; polq *; prc1 *; prr11 *; pttg1 *; racgap1 *; rrm2; rtkn2 *; sema3a; sgol1 *; sgol2 *; shcbp1 *; spag5 *; spc25 *; stil *; top2a *; tpx2 *; troap *; ttk *; ube2c *; xrcc2 * | GO Terms: cell cycle mitosis cytokinesis DDR |
p53RGs (12) ** MVA | up-regulated acat2 **; dhcr7 **; dhcr24 **; fasn **; fdft1 **; fdps **; lpin1 **; lss **; mvd **; nsdhl **; sc4mol **; tm7sf2 ** | GO Terms: lipid metabolism cholesterol- biosynthesis |
ClQ_DEGs_G112 (R273H-p53) | ||
---|---|---|
p53RGs (9) * p21-DREAM | down-regulated: ccnb1 *; dlgap5 *; exo1 *, kif4a *; kif20a *; kif23 *; neil3 *; sema3a; top2a * | GO Terms: cell cycle mitosis cytokinesis DDR |
p53RGs (7) ** MVA | up-regulated: dhcr7 **; fasn **; fdps **; hmgcr **; hmgcs1 **; lss **; sc4mol ** | GO Terms: lipid metabolism cholesterol- biosynthesis |
ClQ_DEGs_#1095 (p53 null) | ||
---|---|---|
p53RGs (0) * GB promotion | down-regulated: arhgap29 *; id1 *; id3 *; igfbp5 *; itga3 * tnfaip3 *; trdc | GO Terms: receptor activity migration |
p53RGs (0) * GB promotion | up-regulated: acsl6 *; bhlhe41; cryab *; ddit4l *; fabp3 *; fn3k; gdf15 *; gpnmb *; lipg; lrrc39; nckap5 *; pcsk6 *; pfkfb2 *; pi15; pnliprp3; serinc5; st3gal5 * | GO Terms: proliferation metabolism |
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Müller, A.; Weyerhäuser, P.; Berte, N.; Jonin, F.; Lyubarskyy, B.; Sprang, B.; Kantelhardt, S.R.; Salinas, G.; Opitz, L.; Schulz-Schaeffer, W.; et al. Concurrent Activation of Both Survival-Promoting and Death-Inducing Signaling by Chloroquine in Glioblastoma Stem Cells: Implications for Potential Risks and Benefits of Using Chloroquine as Radiosensitizer. Cells 2023, 12, 1290. https://doi.org/10.3390/cells12091290
Müller A, Weyerhäuser P, Berte N, Jonin F, Lyubarskyy B, Sprang B, Kantelhardt SR, Salinas G, Opitz L, Schulz-Schaeffer W, et al. Concurrent Activation of Both Survival-Promoting and Death-Inducing Signaling by Chloroquine in Glioblastoma Stem Cells: Implications for Potential Risks and Benefits of Using Chloroquine as Radiosensitizer. Cells. 2023; 12(9):1290. https://doi.org/10.3390/cells12091290
Chicago/Turabian StyleMüller, Andreas, Patrick Weyerhäuser, Nancy Berte, Fitriasari Jonin, Bogdan Lyubarskyy, Bettina Sprang, Sven Rainer Kantelhardt, Gabriela Salinas, Lennart Opitz, Walter Schulz-Schaeffer, and et al. 2023. "Concurrent Activation of Both Survival-Promoting and Death-Inducing Signaling by Chloroquine in Glioblastoma Stem Cells: Implications for Potential Risks and Benefits of Using Chloroquine as Radiosensitizer" Cells 12, no. 9: 1290. https://doi.org/10.3390/cells12091290
APA StyleMüller, A., Weyerhäuser, P., Berte, N., Jonin, F., Lyubarskyy, B., Sprang, B., Kantelhardt, S. R., Salinas, G., Opitz, L., Schulz-Schaeffer, W., Giese, A., & Kim, E. L. (2023). Concurrent Activation of Both Survival-Promoting and Death-Inducing Signaling by Chloroquine in Glioblastoma Stem Cells: Implications for Potential Risks and Benefits of Using Chloroquine as Radiosensitizer. Cells, 12(9), 1290. https://doi.org/10.3390/cells12091290