Interception of Signaling Circuits of Esophageal Adenocarcinoma Cells by Resveratrol Reveals Molecular and Immunomodulatory Signatures

Deregulation of signaling pathways due to mutations sets the cell on a path to neoplasia. Therefore, recent reports of increased mutations observed in esophageal tissue reflects the enhanced risk of tumor formation. In fact, adenocarcinoma of the esophagus has been on the rise lately. Increase in mo...

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Autores principales:	Hardika Dhir, Monica Choudhury, Ketki Patil, Candice Cheung, Adriana Bodlak, Danny Pardo, Asana Adams, Stefano Travaglino, Jose Araque Rojas, S. Balakrishna Pai
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	esophageal adenocarcinoma resveratrol OE33 OE19 FLO-1 apoptosis Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/ef7b704849a94eb0addb35bd182307cc
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spelling	oai:doaj.org-article:ef7b704849a94eb0addb35bd182307cc2021-11-25T17:04:23ZInterception of Signaling Circuits of Esophageal Adenocarcinoma Cells by Resveratrol Reveals Molecular and Immunomodulatory Signatures10.3390/cancers132258112072-6694https://doaj.org/article/ef7b704849a94eb0addb35bd182307cc2021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/22/5811https://doaj.org/toc/2072-6694Deregulation of signaling pathways due to mutations sets the cell on a path to neoplasia. Therefore, recent reports of increased mutations observed in esophageal tissue reflects the enhanced risk of tumor formation. In fact, adenocarcinoma of the esophagus has been on the rise lately. Increase in mortality due to a paucity of efficacious drugs for this cancer prompted us to discover molecular signatures to combat this malady. To this end, we chose resveratrol—a polyphenol with anticancer property—and studied its impact on three esophageal adenocarcinoma cell lines (OE33, OE19 and FLO-1) by multilevel profiling. Here, we show the impact of resveratrol on the viability of the three adenocarcinoma esophageal cell systems studied, at the cellular level. Furthermore, an analysis at the molecular level revealed that the action was through the programmed cell death pathway, resulting in an increase in apoptotic and caspase-positive cells. The impact on reactive oxygen species (ROS) and a decrease in Bcl2 levels were also observed. Moreover, proteomic profiling highlighted pivotal differentially regulated signaling molecules. The phenotypic effect observed in resveratrol-treated esophageal cells could be due to the stoichiometry per se of the fold changes observed in entities of key signaling pathways. Notably, the downregulation of Ku80 and other pivotal entities by resveratrol could be harnessed for chemo-radiation therapy to prevent DNA break repair after radiation therapy. Additionally, multilevel profiling has shed light on molecular and immune-modulatory signatures with implications for discovering novel treatments, including chemo-immunotherapy, for esophageal adenocarcinomas which are known to be aggressive cancers.Hardika DhirMonica ChoudhuryKetki PatilCandice CheungAdriana BodlakDanny PardoAsana AdamsStefano TravaglinoJose Araque RojasS. Balakrishna PaiMDPI AGarticleesophageal adenocarcinomaresveratrolOE33OE19FLO-1apoptosisNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5811, p 5811 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	esophageal adenocarcinoma resveratrol OE33 OE19 FLO-1 apoptosis Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	esophageal adenocarcinoma resveratrol OE33 OE19 FLO-1 apoptosis Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Hardika Dhir Monica Choudhury Ketki Patil Candice Cheung Adriana Bodlak Danny Pardo Asana Adams Stefano Travaglino Jose Araque Rojas S. Balakrishna Pai Interception of Signaling Circuits of Esophageal Adenocarcinoma Cells by Resveratrol Reveals Molecular and Immunomodulatory Signatures
description	Deregulation of signaling pathways due to mutations sets the cell on a path to neoplasia. Therefore, recent reports of increased mutations observed in esophageal tissue reflects the enhanced risk of tumor formation. In fact, adenocarcinoma of the esophagus has been on the rise lately. Increase in mortality due to a paucity of efficacious drugs for this cancer prompted us to discover molecular signatures to combat this malady. To this end, we chose resveratrol—a polyphenol with anticancer property—and studied its impact on three esophageal adenocarcinoma cell lines (OE33, OE19 and FLO-1) by multilevel profiling. Here, we show the impact of resveratrol on the viability of the three adenocarcinoma esophageal cell systems studied, at the cellular level. Furthermore, an analysis at the molecular level revealed that the action was through the programmed cell death pathway, resulting in an increase in apoptotic and caspase-positive cells. The impact on reactive oxygen species (ROS) and a decrease in Bcl2 levels were also observed. Moreover, proteomic profiling highlighted pivotal differentially regulated signaling molecules. The phenotypic effect observed in resveratrol-treated esophageal cells could be due to the stoichiometry per se of the fold changes observed in entities of key signaling pathways. Notably, the downregulation of Ku80 and other pivotal entities by resveratrol could be harnessed for chemo-radiation therapy to prevent DNA break repair after radiation therapy. Additionally, multilevel profiling has shed light on molecular and immune-modulatory signatures with implications for discovering novel treatments, including chemo-immunotherapy, for esophageal adenocarcinomas which are known to be aggressive cancers.
format	article
author	Hardika Dhir Monica Choudhury Ketki Patil Candice Cheung Adriana Bodlak Danny Pardo Asana Adams Stefano Travaglino Jose Araque Rojas S. Balakrishna Pai
author_facet	Hardika Dhir Monica Choudhury Ketki Patil Candice Cheung Adriana Bodlak Danny Pardo Asana Adams Stefano Travaglino Jose Araque Rojas S. Balakrishna Pai
author_sort	Hardika Dhir
title	Interception of Signaling Circuits of Esophageal Adenocarcinoma Cells by Resveratrol Reveals Molecular and Immunomodulatory Signatures
title_short	Interception of Signaling Circuits of Esophageal Adenocarcinoma Cells by Resveratrol Reveals Molecular and Immunomodulatory Signatures
title_full	Interception of Signaling Circuits of Esophageal Adenocarcinoma Cells by Resveratrol Reveals Molecular and Immunomodulatory Signatures
title_fullStr	Interception of Signaling Circuits of Esophageal Adenocarcinoma Cells by Resveratrol Reveals Molecular and Immunomodulatory Signatures
title_full_unstemmed	Interception of Signaling Circuits of Esophageal Adenocarcinoma Cells by Resveratrol Reveals Molecular and Immunomodulatory Signatures
title_sort	interception of signaling circuits of esophageal adenocarcinoma cells by resveratrol reveals molecular and immunomodulatory signatures
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/ef7b704849a94eb0addb35bd182307cc
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Interception of Signaling Circuits of Esophageal Adenocarcinoma Cells by Resveratrol Reveals Molecular and Immunomodulatory Signatures

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