Photodynamic Priming Improves the Anti-Migratory Activity of Prostaglandin E Receptor 4 Antagonist in Cancer Cells In Vitro
The combination of photodynamic agents and biological inhibitors is rapidly gaining attention for its promise and approval in treating advanced cancer. The activity of photodynamic treatment is mainly governed by the formation of reactive oxygen species upon light activation of photosensitizers. Exp...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-10-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/21/5259 |
| _version_ | 1797410941901471744 |
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| author | Aaron J. Sorrin Cindy Liu Julia Cicalo Jocelyn Reader Daniel Najafali Yuji Zhang Dana M. Roque Huang-Chiao Huang |
| author_facet | Aaron J. Sorrin Cindy Liu Julia Cicalo Jocelyn Reader Daniel Najafali Yuji Zhang Dana M. Roque Huang-Chiao Huang |
| author_sort | Aaron J. Sorrin |
| collection | DOAJ |
| description | The combination of photodynamic agents and biological inhibitors is rapidly gaining attention for its promise and approval in treating advanced cancer. The activity of photodynamic treatment is mainly governed by the formation of reactive oxygen species upon light activation of photosensitizers. Exposure to reactive oxygen species above a threshold dose can induce cellular damage and cancer cell death, while the surviving cancer cells are “photodynamically primed”, or sensitized, to respond better to other drugs and biological treatments. Here, we report a new combination regimen of photodynamic priming (PDP) and prostaglandin E<sub>2</sub> receptor 4 (EP4) inhibition that reduces the migration and invasion of two human ovarian cancer cell lines (OVCAR-5 and CAOV3) in vitro. PDP is achieved by red light activation of the FDA-approved photosensitizer, benzoporphyrin derivative (BPD), or a chemical conjugate composed of the BPD linked to cetuximab, an anti-epithelial growth factor receptor (EGFR) antibody. Immunoblotting data identify co-inhibition of EGFR, cAMP-response element binding protein (CREB), and extracellular signal-regulated kinase 1/2 (ERK1/2) as key in the signaling cascades modulated by the combination of EGFR-targeted PDP and EP4 inhibition. This study provides valuable insights into the development of a molecular-targeted photochemical strategy to improve the anti-metastatic effects of EP4 receptor antagonists. |
| first_indexed | 2024-03-09T04:37:44Z |
| format | Article |
| id | doaj.art-214d0fb3e1ff47809700e030cc775f90 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T04:37:44Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-214d0fb3e1ff47809700e030cc775f902023-12-03T13:24:45ZengMDPI AGCancers2072-66942021-10-011321525910.3390/cancers13215259Photodynamic Priming Improves the Anti-Migratory Activity of Prostaglandin E Receptor 4 Antagonist in Cancer Cells In VitroAaron J. Sorrin0Cindy Liu1Julia Cicalo2Jocelyn Reader3Daniel Najafali4Yuji Zhang5Dana M. Roque6Huang-Chiao Huang7Fischell Department of Bioengineering, University of Maryland, College Park, MD 20742, USAFischell Department of Bioengineering, University of Maryland, College Park, MD 20742, USAFischell Department of Bioengineering, University of Maryland, College Park, MD 20742, USADepartment of Obstetrics, Gynecology, and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USAFischell Department of Bioengineering, University of Maryland, College Park, MD 20742, USAUniversity of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, MD 21201, USADepartment of Obstetrics, Gynecology, and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USAFischell Department of Bioengineering, University of Maryland, College Park, MD 20742, USAThe combination of photodynamic agents and biological inhibitors is rapidly gaining attention for its promise and approval in treating advanced cancer. The activity of photodynamic treatment is mainly governed by the formation of reactive oxygen species upon light activation of photosensitizers. Exposure to reactive oxygen species above a threshold dose can induce cellular damage and cancer cell death, while the surviving cancer cells are “photodynamically primed”, or sensitized, to respond better to other drugs and biological treatments. Here, we report a new combination regimen of photodynamic priming (PDP) and prostaglandin E<sub>2</sub> receptor 4 (EP4) inhibition that reduces the migration and invasion of two human ovarian cancer cell lines (OVCAR-5 and CAOV3) in vitro. PDP is achieved by red light activation of the FDA-approved photosensitizer, benzoporphyrin derivative (BPD), or a chemical conjugate composed of the BPD linked to cetuximab, an anti-epithelial growth factor receptor (EGFR) antibody. Immunoblotting data identify co-inhibition of EGFR, cAMP-response element binding protein (CREB), and extracellular signal-regulated kinase 1/2 (ERK1/2) as key in the signaling cascades modulated by the combination of EGFR-targeted PDP and EP4 inhibition. This study provides valuable insights into the development of a molecular-targeted photochemical strategy to improve the anti-metastatic effects of EP4 receptor antagonists.https://www.mdpi.com/2072-6694/13/21/5259prostaglandin inhibitorphotoimmunotherapyantibody-drug conjugateovarian cancerphotodynamic therapy |
| spellingShingle | Aaron J. Sorrin Cindy Liu Julia Cicalo Jocelyn Reader Daniel Najafali Yuji Zhang Dana M. Roque Huang-Chiao Huang Photodynamic Priming Improves the Anti-Migratory Activity of Prostaglandin E Receptor 4 Antagonist in Cancer Cells In Vitro Cancers prostaglandin inhibitor photoimmunotherapy antibody-drug conjugate ovarian cancer photodynamic therapy |
| title | Photodynamic Priming Improves the Anti-Migratory Activity of Prostaglandin E Receptor 4 Antagonist in Cancer Cells In Vitro |
| title_full | Photodynamic Priming Improves the Anti-Migratory Activity of Prostaglandin E Receptor 4 Antagonist in Cancer Cells In Vitro |
| title_fullStr | Photodynamic Priming Improves the Anti-Migratory Activity of Prostaglandin E Receptor 4 Antagonist in Cancer Cells In Vitro |
| title_full_unstemmed | Photodynamic Priming Improves the Anti-Migratory Activity of Prostaglandin E Receptor 4 Antagonist in Cancer Cells In Vitro |
| title_short | Photodynamic Priming Improves the Anti-Migratory Activity of Prostaglandin E Receptor 4 Antagonist in Cancer Cells In Vitro |
| title_sort | photodynamic priming improves the anti migratory activity of prostaglandin e receptor 4 antagonist in cancer cells in vitro |
| topic | prostaglandin inhibitor photoimmunotherapy antibody-drug conjugate ovarian cancer photodynamic therapy |
| url | https://www.mdpi.com/2072-6694/13/21/5259 |
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