Unveiling the Molecular Mechanisms Driving the Capsaicin-Induced Immunomodulatory Effects on PD-L1 Expression in Bladder and Renal Cancer Cell Lines
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Cell Lines
2.2. Reagents
2.3. MTT Assay
2.4. ROS Analysis
2.5. Mitochondrial Transmembrane Potential (∆Ψm) Assay
2.6. Annexin V and PI Staining
2.7. Western Blot Analysis
2.8. RT Profiler PCR Array
2.9. Confocal Laser Scanning Microscopy Analysis
2.10. Oxidized Protein Analysis
2.11. TRPV1 Silencing
2.12. Statistical Analysis
3. Results
3.1. CPS Induces DNA Damage in Living 5637, T24 and A498 Cancer Cell Lines
3.2. CPS-Induced DNA Damage Modulates the PD-L1 mRNA and Protein Expression in T24, 5637 and A498 Cells
3.3. Distribution of PD-L1 Protein in CPS-Treated T24, 5637 and A498 Cells
3.4. CPS-Induced DSB DNA Damage Is Associated with p53/ATM/CHK2 and BRCA1/hTERT mRNA Expression in T24, 5637 and A498 Cells
3.5. TRPV1- or ROS-Dependent Signals Induced in CPS-Treated T24, 5637 and A498 Cells
3.6. Transcriptional Factors, Oncogenes, Cytokines and Growth Factors Are Associated Gene-Promoting Drivers in CPS-Induced Modulation of PD-L1 Expression in 5637, T24 and A498 Cells
3.7. Nucleoside Diphosphate Kinase (NDPK)/Nm23-H4 Played a Role in the CPS-Induced PD-L1 Protein Expression Modulation in T24 and 5637 Cells
3.8. CPS-Induced PD-L1 Modulation Requires Stat1/Stat3 Activation in 5637, T24 and A498 Cells
4. Discussion
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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Unigene | GenBank ID | Symbol | Cell Lines | |||||
---|---|---|---|---|---|---|---|---|
5637 | T24 | A498 | ||||||
4 h | 12 h | 4 h | 12 h | 4 h | 12 h | |||
NM_003998 | Nuclear factor of kappa light polypeptide gene enhancer in B cells-1 | NF-kB1 | 1.4 | −1.2 | 1.1 | −1.8 | 2.0 * | −1.2 |
NM_020529 | Nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor alpha | NF-kBIA | −2.3 * | −2.7 * | −2.1 * | −1.7 | −1.2 | −1.7 |
NM_005225 | E2F transcriptional factor 1 | E2F1 | N/A | N/A | N/A | N/A | IND * | 3.2 * |
NM_005239 | V-ETs erythroblastosis virus E26 oncogene homolog 2 | ETS2 | −1.1 | −2.2 * | −1.0 | −2.8 * | 1.7 | −1.2 |
NM_005252 | V-Fos FBJ murine osteosarcoma viral oncogene homolog | FOS | −1.4 | −3.0 * | −1.9 | −2.0 * | −2.3* | −7.7 * |
NM_002228 | V-Jun sarcoma virus 17 oncogene homolog | JUN | −1.3 | −2.4 * | −1.1 | −2.8 * | −2.6* | −3.1 * |
NM_002467 | V-mycmyelocitomatosis viral oncogene | MYC | 1.3 | −1.5 | 1.5 | −1.9 | 5.0 * | 2.0 * |
NM−005163 | V-Akt murine thymoma viral oncogene homolog 1 | AKT | SIL * | −2.9 * | −2.3 * | −3.4 * | N/A | N/A |
NM_004448 | V-Erb-b2 erythroblastic leukemia viral oncogene homolog 2 | ERBB2 | 1.1 | −2.4 * | 1.1 | −2.4 * | 3.2 * | 1.5 |
NM_002880 | V-Raf-1 murine leukemia viral oncogene homolog 1 | RAF1 | 1.0 | −1.2 | 1.1 | −1.0 | 1.5 | 1.2 |
NM_000245 | Met proto-oncogene | MET | N/A | N/A | N/A | N/A | IND * | 1.9 |
NM-002755 | Mitogen-activated protein kinase kinase 1 | MAPKK1 | −2.6 * | −1.4 | −2.4 * | −1.0 | 2.7 * | 2.0 * |
NM_181504 | Phosphoinositide-3-kinase, regulatory subunit polypeptide 1 | PI3K | 1.6 | 1.1 | 1.8 | 1.6 | 1.0 | −1.1 |
NM_003177 | Spleen tyrosine kinase | SYK | N/A | N/A | N/A | N/A | IND * | 2.8 * |
Unigene | GenBank ID | Symbol | Cell Lines | |||||
---|---|---|---|---|---|---|---|---|
5637 | T24 | A498 | ||||||
4 h | 12 h | 4 h | 12 h | 4 h | 12 h | |||
NM_024013 | Interferon alpha 1 | IFN-α1 | 17.4 * | 12.2 * | 6.2 * | 4.9 * | 1.5 | 1.6 |
NM_002176 | Interferon beta 1 fibroblast | IFN-β1 | 24.5 * | 19.8 * | 9.5 * | 5.3 * | 1.4 | 1.3 |
NM_000618 | Insulin-like growth factor 1 | IGF-1 | N/A | N/A | N/A | N/A | N/A | N/A |
NM_000584 | Interleukin-8 | IL-8 | 1.3 | 1.1 | 1.1 | −9.1 * | 1.8 | 1.1 |
NM_002607 | Platelet-derived growth factor alpha polypeptide | PDGF-A | N/A | N/A | N/A | N/A | IND * | 3.0 * |
NM_002607 | Platelet-derived growth factor beta polypeptide | PDGF-B | −1.1 | −1.5 | −1.7 | −1.9 | −3.7 * | −3.9 * |
NM_000660 | Transforming growth factor beta-1 | TGF-β1 | 1.1 | 1.0 | 1.2 | 2.5 * | 1.5 | 4.0 * |
NM_000594 | Tumor necrosis factor alpha | TNF-α | 1.9 | 1.7 | 1.4 | −1.6 | 2.9 * | 2.0 * |
NM_000141 | Fibroblast growth factor receptor 2 | FGFR2 | 2.3 * | −1.3 | 2.3 * | −1.3 | 1.5 | 1.1 |
NM_003246 | Transforming growth factor beta receptor 1 | TGFβR1 | 1.0 | 1.2 | 1.6 | 2.1 * | 2.0 * | 2.2 * |
NM_003862 | Tumor necrosis factor receptor superfamily member 10b | TNFRSM10b | −1.4 | −2.4 * | −1.4 | −2.4 * | 2.8 * | 1.6 |
NM_001065 | Tumor necrosis factor receptor superfamily member 1A | TNFRSM1A | −2.0 * | −3.6 * | −2.0 * | −3.6 * | 2.0 * | 1.1 |
NM_003790 | Tumor necrosis factor receptor superfamily member 25 | TNFRSM25 | 1.7 | −1.6 | 1.7 | −1.6 | 2.8 * | 2.0 * |
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Morelli, M.B.; Marinelli, O.; Aguzzi, C.; Zeppa, L.; Nabissi, M.; Amantini, C.; Tomassoni, D.; Maggi, F.; Santoni, M.; Santoni, G. Unveiling the Molecular Mechanisms Driving the Capsaicin-Induced Immunomodulatory Effects on PD-L1 Expression in Bladder and Renal Cancer Cell Lines. Cancers 2022, 14, 2644. https://doi.org/10.3390/cancers14112644
Morelli MB, Marinelli O, Aguzzi C, Zeppa L, Nabissi M, Amantini C, Tomassoni D, Maggi F, Santoni M, Santoni G. Unveiling the Molecular Mechanisms Driving the Capsaicin-Induced Immunomodulatory Effects on PD-L1 Expression in Bladder and Renal Cancer Cell Lines. Cancers. 2022; 14(11):2644. https://doi.org/10.3390/cancers14112644
Chicago/Turabian StyleMorelli, Maria Beatrice, Oliviero Marinelli, Cristina Aguzzi, Laura Zeppa, Massimo Nabissi, Consuelo Amantini, Daniele Tomassoni, Federica Maggi, Matteo Santoni, and Giorgio Santoni. 2022. "Unveiling the Molecular Mechanisms Driving the Capsaicin-Induced Immunomodulatory Effects on PD-L1 Expression in Bladder and Renal Cancer Cell Lines" Cancers 14, no. 11: 2644. https://doi.org/10.3390/cancers14112644