Withametelin inhibits TGF-β induced Epithelial-to-Mesenchymal Transition and Programmed-Death Ligand-1 expression .

Withanolides are a group of naturally occurring plant-based small molecules known for their wide range of host cellular functions. The anticancer potential of withanolides has been explored in varying cancer cell lines . Based on our prior studies, among the tested withanolides, withametelin (WM) has shown significant cytotoxicity with the highest efficacy on HCT-116 colon cancer cells (IC 0.719 ± 0.12μM). Treatment with WM reduced the TGF-β driven proliferation, colony-forming ability, migration, and invasiveness of HCT-116 cells . WM also downregulated the expression of mesenchymal markers such as N-CADHERIN, SNAIL, and SLUG in HCT-116 cells. At the molecular level, WM inhibited TGF-β induced phosphorylation of SMAD2/3 and reduced the expression of an immune checkpoint inhibitor programmed-death ligand-1 (PD-L1). Our study highlights the possible anticancer mechanisms of WM involving modulation of the TGF-β pathway and associated target gene expression, suggesting its potential utility in cancer therapy.