Title: Detection of ellagic acid at the intracellular level led to the design of mimetic of ellagic acid (MEA) as potential inhibitor of c-Raf and c-Ras
Abstract:
The side effects of existing drugs and other methods, which are effective in decreasing the progression of cancer, are quite harmful and toxic to our bodies. To tackle this, a safer method needs to be derived. Dietary and their gut metabolized chemicals are being explored for inhibitory roles in cancer cells. In essence, mimetic metabolites is conceived as a potential source of a new class of anticancer drugs. Anticancer compositions of ellagic acid enriched compositions were prepared and processed in our lab. We have employed a novel vertical tube gel electrophoresis (VTGE) assisted and LC-HRMS-based intracellular metabolite profiling approach to detect metabolites/chemicals in HCT-116 cells treated by ellagic acid enriched compositions. Furthermore, we used molecular docking and molecular dynamics (MD) simulations to assess the inhibitory role of ellagic acid and mimetic of ellagic acid (MEA)upon various intracellular oncoproteins including c-Raf and c-RAS. We also performed ADMET profiling of ellagic acid and their mimetic to assess their toxicity profile using vNN-ADMET and SwissADME. Ellagic acid-enriched compositions showed appreciable cell death in HCT-116 and MCF-7 cancer cells. Intracellular profiling of cancer cells indicated the presence of ellagic acid, a metabolized product of ellagitannins. Molecular docking data suggested the specific and strong binding upon a key intracellular RAS and c-Raff kinase among several screened intracellular proteins. MD simulations data strengthened the possibilities with revelations on the inhibitory of MEA with a comparison to known Ras inhibitor, salirasib and c-Raf kinase inhibitors. Further, ADMET predictions showed that ellagic acid is safer than known inhibitors and can be used safely at higher concentrations as well. MEA, a metabolized dietary chemical, could be explored as an inhibitor of c-Ras and c-Raf kinase oncoprotein as potential anticancer agents.
Audience Take Away Notes :
- This presentation will help to understand the importance of mimetic of ellagic acid as a potential anticancer agent.
- In the future, preclinical and clinical studies by other researchers will be encouraged
