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

Abstract

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.

Deoxyhypusine synthase mutations alter the post-translational modification of eukaryotic initiation factor 5A resulting in impaired human and mouse neural homeostasis

“…Sample preparation was adapted from previous publications. 25 , 26 , 27 In brief, approximately 10 million cells were collected from each LCL to be analyzed, washed with PBS, lysed in 2-D cell lysis buffer (Applied Biomics) and quantified for protein concentration (Bio-Rad). Control and experimental samples were labeled with either Cy3 or Cy5 dyes.…”

Multifaceted Effects of Kinase Inhibitors on Pancreatic Cancer Cells Reveals Pivotal Entities with Therapeutic Implications

“…Proteomic analysis was performed by 2D DIGE and mass spectrometry, which was conducted by Applied Biomics Inc. (Hayward, CA, USA) employing previously published methodologies [ 27 ]. PANC-1 cells were treated individually with 8 µM AT or 5 µM WZ.…”

“…Cells from control samples and treated samples were collected, washed with 1×PBS, and then stored at −80 °C prior to sending the samples to Applied Biomics Inc. (Hayward, CA, USA) on dry ice for proteomic analysis. The protocol performed was as described previously [ 27 , 28 , 29 ]. STRING database version 11.5 was used to perform functional enrichment analysis and to generate protein–protein interaction networks [ 30 ].…”

Stand Up to Stand Out: Natural Dietary Polyphenols Curcumin, Resveratrol, and Gossypol as Potential Therapeutic Candidates against Severe Acute Respiratory Syndrome Coronavirus 2 Infection

“…Resveratrol (RSV), a polyphenolic nutraceutical mainly found in grapes ( Vitis vinifera L.) ( Figure 3 ), demonstrates health-promoting properties, including antioxidative [ 61 ], immunomodulatory [ 62 ], and anti-aging effects [ 63 ]. Since its association with the “French paradox” in 1992, resveratrol has received increasing research interest owing to its diverse pharmacological activities and multi-organ protective effects (e.g., acute lung injury [ 64 ], cerebral ischemia/reperfusion injury [ 65 ], myocardial cell apoptosis [ 66 ], and hepatic injury [ 67 ]).…”