A chalcone derivative retards renal cyst enlargement by inhibiting fluid secretion and cell proliferation in an in vitro model of polycystic kidney disease

Veeraphan, Peerachat; Chavasiri, Warinthorn; Muanprasat, Chatchai; Chatsudthipong, Varanuj; Yuajit, Chaowalit

doi:10.1007/s10157-021-02080-1

Cited by 2 publications

(3 citation statements)

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“…We demonstrated that GA (2.5 µM) can upregulate the AMPK level both in MDCK and Pkd1 mutant cell monolayers (Figure 4). Previous studies have reported that chitosan oligosaccharide and chalcone derivative can retard MDCK cyst progression by activating AMPK [23,24]. To support this finding, previous studies reported that GA can inhibit glioma cells by activating AMPK, which inhibits the AKT/mTOR pathways [19].…”

Section: Discussionmentioning

confidence: 78%

“…Since PKD pathophysiology involves abnormal cyst-lining epithelial cell proliferation, as well as fluid secretion pathways, a compound that inhibits these pathways could markedly retard renal cystogenesis both in an in vitro and in vivo model of PKD. Several natural compounds have been found to retard renal cystogenesis via the inhibition of cell proliferation (i.e., steviol, curcumin, ginkgolide B, chitosan, chalcone) [23][24][25][26][27]. However, other compounds with high potency, low concentration, and multitargets are still needed.…”

Section: Discussionmentioning

confidence: 99%

“…After treatment with GA, it was found that GA (0.25-2.5 µM) markedly retarded MDCK cyst progression (Figure 1c-e). Our previous studies showed that natural compounds such as steviol and chalcone derivative can slow MDCK cyst enlargement at a dose of 50-100 µM [24,28]. Interestingly, the effective dose of GA (0.25-2.5 µM) to retard MDCK cyst growth was very low compared to steviol and chalcone.…”

Section: Discussionmentioning

confidence: 99%

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Potential Application of Gambogic Acid for Retarding Renal Cyst Progression in Polycystic Kidney Disease

et al. 2022

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Abnormal cell proliferation and accumulation of fluid-filled cysts along the nephrons in polycystic kidney disease (PKD) could lead to a decline in renal function and eventual end-stage renal disease (ESRD). Gambogic acid (GA), a xanthone compound extracted from the brownish resin of the Garcinia hanburyi tree, exhibits various pharmacological properties, including anti-inflammation, antioxidant, anti-proliferation, and anti-cancer activity. However, its effect on inhibiting cell proliferation in PKD is still unknown. This study aimed to determine the pharmacological effects and detailed mechanisms of GA in slowing an in vitro cyst growth model of PKD. The results showed that GA (0.25–2.5 μM) significantly retarded MDCK cyst growth and cyst formation in a dose-dependent manner, without cytotoxicity. Using the BrdU cell proliferation assay, it was found that GA (0.5–2.5 μM) suppressed MDCK and Pkd1 mutant cell proliferation. In addition, GA (0.5–2.5 μM) strongly inhibited phosphorylation of ERK1/2 and S6K expression and upregulated the activation of phosphorylation of AMPK, both in MDCK cells and Pkd1 mutant cells. Taken together, these findings suggested that GA could retard MDCK cyst enlargement, at least in part by inhibiting the cell proliferation pathway. GA could be a natural plant-based drug candidate for ADPKD intervention.

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Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Potential Application of Gambogic Acid for Retarding Renal Cyst Progression in Polycystic Kidney Disease

et al. 2022

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The Cystic Fibrosis Transmembrane Conductance Regulator Gene (CFTR) Is under Post-Transcriptional Control of microRNAs: Analysis of the Effects of agomiRNAs Mimicking miR-145-5p, miR-101-3p, and miR-335-5p

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et al. 2023

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(1) Background: MicroRNAs are involved in the expression of the gene encoding the chloride channel CFTR (Cystic Fibrosis Transmembrane Conductance Regulator); the objective of this short report is to study the effects of the treatment of bronchial epithelial Calu-3 cells with molecules mimicking the activity of pre-miR-145-5p, pre-miR-335-5p, and pre-miR-101-3p, and to discuss possible translational applications of these molecules in pre-clinical studies focusing on the development of protocols of possible interest in therapy; (2) Methods: CFTR mRNA was quantified by Reverse Transcription quantitative Polymerase Chain Reaction (RT-qPCR). The production of the CFTR protein was assessed by Western blotting; (3) Results: The treatment of Calu-3 cells with agomiR-145-5p caused the highest inhibition of CFTR mRNA accumulation and CFTR production; (4) Conclusions: The treatment of target cells with the agomiR pre-miR-145-5p should be considered when CFTR gene expression should be inhibited in pathological conditions, such as polycystic kidney disease (PKD), some types of cancer, cholera, and SARS-CoV-2 infection.

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A chalcone derivative retards renal cyst enlargement by inhibiting fluid secretion and cell proliferation in an in vitro model of polycystic kidney disease

Cited by 2 publications

References 25 publications

Potential Application of Gambogic Acid for Retarding Renal Cyst Progression in Polycystic Kidney Disease

Potential Application of Gambogic Acid for Retarding Renal Cyst Progression in Polycystic Kidney Disease

The Cystic Fibrosis Transmembrane Conductance Regulator Gene (CFTR) Is under Post-Transcriptional Control of microRNAs: Analysis of the Effects of agomiRNAs Mimicking miR-145-5p, miR-101-3p, and miR-335-5p

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