ArticleClinical and experimental nephrology2021
A chalcone derivative retards renal cyst enlargement by inhibiting fluid secretion and cell proliferation in an in vitro model of polycystic kidney disease.
Article in Clinical and experimental nephrology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3 citing papers in PubMed, 3 citations in OpenAlex.
- Nephroprotective Activity ofDrug design, development and therapy · 2024Article
- Article
- Potential Application of Gambogic Acid for Retarding Renal Cyst Progression in Polycystic Kidney Disease.Molecules (Basel, Switzerland) · 2022Article
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5 authors at 4 institutions in 1 country.
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Abstract
backgroundRenal bilateral fluid filled-cyst in polycystic kidney disease (PKD) is associated with abnormal epithelial cell proliferation and transepithelial fluid secretion which leads to end-stage renal disease (ESRD). A chalcone derivative, isoliquiritigenin (ISLQ), has been shown to have various pharmacological properties. Since several studies have shown that ISLQ could inhibit CFTR channel activity, it is interesting to see whether it can inhibit renal cyst enlargement. The present study was aimed to determine an inhibitory effect and the mechanism of chalcone derivatives on MDCK cyst progression and Pkd1 mutant cells.
methodsMDCK cyst growth and cyst formation experiments, MTT assay, Ussing chamber experiment, BrdU cell proliferation assay and western blot analysis were performed in this study.
resultsAmong four compounds of chalcone derivatives tested, CHAL-005 (100 µM) was found to inhibit MDCK cyst growth in a dose-dependent manner without cytotoxicity. It inhibited short-circuit current of chloride secretion as well as CFTR protein expression in MDCK cells. CHAL-005 significantly suppressed cell proliferation. In addition, CHAL-005 strongly reduced phosphorylation ERK1/2 and phosphorylation S6 kinase in MDCK and Pkd1 mutant cells. Interestingly, CHAL-005 activated phosphorylation of AMP kinase protein expression in MDCK and Pkd1 mutant cells.
conclusionCHAL-005 slowed MDCK cyst progression by inhibiting CFTR expression and reducing ERK1/2 and mTOR/S6K signaling pathways as well as activating AMPK expression. Therefore, a chalcone derivative could represent as a promising drug candidate for polycystic kidney disease intervention.
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