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...

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Autores principales:	Aaron J. Sorrin, Cindy Liu, Julia Cicalo, Jocelyn Reader, Daniel Najafali, Yuji Zhang, Dana M. Roque, Huang-Chiao Huang
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	prostaglandin inhibitor photoimmunotherapy antibody-drug conjugate ovarian cancer photodynamic therapy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/214d0fb3e1ff47809700e030cc775f90
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spelling	oai:doaj.org-article:214d0fb3e1ff47809700e030cc775f902021-11-11T15:26:36ZPhotodynamic Priming Improves the Anti-Migratory Activity of Prostaglandin E Receptor 4 Antagonist in Cancer Cells In Vitro10.3390/cancers132152592072-6694https://doaj.org/article/214d0fb3e1ff47809700e030cc775f902021-10-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5259https://doaj.org/toc/2072-6694The 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.Aaron J. SorrinCindy LiuJulia CicaloJocelyn ReaderDaniel NajafaliYuji ZhangDana M. RoqueHuang-Chiao HuangMDPI AGarticleprostaglandin inhibitorphotoimmunotherapyantibody-drug conjugateovarian cancerphotodynamic therapyNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5259, p 5259 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	prostaglandin inhibitor photoimmunotherapy antibody-drug conjugate ovarian cancer photodynamic therapy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	prostaglandin inhibitor photoimmunotherapy antibody-drug conjugate ovarian cancer photodynamic therapy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 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
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.
format	article
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
title	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_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_sort	photodynamic priming improves the anti-migratory activity of prostaglandin e receptor 4 antagonist in cancer cells in vitro
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/214d0fb3e1ff47809700e030cc775f90
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Photodynamic Priming Improves the Anti-Migratory Activity of Prostaglandin E Receptor 4 Antagonist in Cancer Cells In Vitro

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