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Article

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

Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 313 Ferst Drive, Atlanta, GA 30332, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally.
Academic Editor: Alexander Quaas
Cancers 2021, 13(22), 5811; https://doi.org/10.3390/cancers13225811
Received: 9 October 2021 / Revised: 12 November 2021 / Accepted: 17 November 2021 / Published: 19 November 2021
(This article belongs to the Special Issue Current and Future Treatment Strategies for Esophageal Adenocarcinoma)
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 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 cell systems studied, at the cellular, molecular level and by proteomic analysis. Impact on programmed cell death pathway resulting in an increase in apoptotic and caspase-positive cells were observed. Decrease in Bcl2. levels and impact on reactive oxygen species (ROS) was also observed. Moreover, proteomic profiling highlighted pivotal differentially regulated signaling molecules. Notably, the downregulation of Ku80 by resveratrol could be harnessed for chemo-radiation therapy to prevent DNA break repair after radiation therapy. Additionally, protein profiling has shed light on molecular and immune-modulatory signatures with implications for discovering novel treatments such as chemo-immunotherapy.
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. View Full-Text
Keywords: esophageal adenocarcinoma; resveratrol; OE33; OE19; FLO-1; apoptosis; caspases; Bcl2; proteomics; flow cytometry esophageal adenocarcinoma; resveratrol; OE33; OE19; FLO-1; apoptosis; caspases; Bcl2; proteomics; flow cytometry
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MDPI and ACS Style

Dhir, H.; Choudhury, M.; Patil, K.; Cheung, C.; Bodlak, A.; Pardo, D.; Adams, A.; Travaglino, S.; Rojas, J.A.; Pai, S.B. Interception of Signaling Circuits of Esophageal Adenocarcinoma Cells by Resveratrol Reveals Molecular and Immunomodulatory Signatures. Cancers 2021, 13, 5811. https://doi.org/10.3390/cancers13225811

AMA Style

Dhir H, Choudhury M, Patil K, Cheung C, Bodlak A, Pardo D, Adams A, Travaglino S, Rojas JA, Pai SB. Interception of Signaling Circuits of Esophageal Adenocarcinoma Cells by Resveratrol Reveals Molecular and Immunomodulatory Signatures. Cancers. 2021; 13(22):5811. https://doi.org/10.3390/cancers13225811

Chicago/Turabian Style

Dhir, Hardika, Monica Choudhury, Ketki Patil, Candice Cheung, Adriana Bodlak, Danny Pardo, Asana Adams, Stefano Travaglino, Jose A. Rojas, and S. B. Pai. 2021. "Interception of Signaling Circuits of Esophageal Adenocarcinoma Cells by Resveratrol Reveals Molecular and Immunomodulatory Signatures" Cancers 13, no. 22: 5811. https://doi.org/10.3390/cancers13225811

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