Resveratrol downregulates ENaCs through the activation of AMPK in human colon cancer cells.

Epithelial sodium channels (ENaCs) are critically engaged in a number of hallmarks of cancer progression, including proliferation, migration, invasion and apoptosis. Thus, the inhibition of ENaCs possesses therapeutic potential in cancer. Resveratrol, a natural polyphenol with anti-carcinogenic activity, is a potent activator of 5' AMP-activated protein kinase (AMPK) which reduces the abundance of ENaCs in the cell membrane by causing the internalization of the β subunit. However, the effect of resveratrol on ENaCs in cancer cells is unknown. Therefore, in this study, we aimed to investigate the effects of resveratrol on ENaCs in human colon cancer cells HCT116 and HT29. The influences of resveratrol either alone or together with AMPK inhibitor compound C (CC), and ENaC inhibitor amiloride on cell viability were examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The expression levels of phospho-AMPK Thr172 and βENaC in cells were determined by immunofluorescence staining, and the expression of apoptotic markers Caspase-3 and Caspase-9 were analyzed by qRT-PCR. Resveratrol was found to activate AMPK in a dose-dependent manner. Both AMPK activation by resveratrol and ENaC inhibition by amiloride decreased cell viability and increased apoptosis significantly. AMPK activation also reduced βENaC expression in cells. Our results suggest that ENaC inhibition through AMPK activation might be a potential mechanism underlying the anti-cancer effects of resveratrol.

• Publication year

  2023

• Venue

  Tissue & Cell

• Publication date

  2023-03-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/j.tice.2023.102071PMID 36965273
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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