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

Autor: Fathima A; Cell Signaling Laboratory, Department of Biological Sciences, Birla Institute of Technology & Science, Hyderabad, India., Farboodniay Jahromi MA; Medicinal Plants Processing Research Center, Shiraz University of Medical Sciences, Shiraz, Iran., Begum SA; Department of Pharmacy, Birla Institute of Technology & Science, Hyderabad, India., Jamma T; Cell Signaling Laboratory, Department of Biological Sciences, Birla Institute of Technology & Science, Hyderabad, India.
Jazyk: angličtina
Zdroj: Frontiers in oncology [Front Oncol] 2024 Jul 15; Vol. 14, pp. 1435516. Date of Electronic Publication: 2024 Jul 15 (Print Publication: 2024).
DOI: 10.3389/fonc.2024.1435516
Abstrakt: 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 in vitro . 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 50 0.719 ± 0.12μM). Treatment with WM reduced the TGF-β driven proliferation, colony-forming ability, migration, and invasiveness of HCT-116 cells in vitro . 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.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2024 Fathima, Farboodniay Jahromi, Begum and Jamma.)
Databáze: MEDLINE
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