Berberine slows cell growth in autosomal dominant polycystic kidney disease cells

Journal Article · Fri Nov 22 04:00:00 EST 2013 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2013.10.076· OSTI ID:22242199

Bonon, Anna; Mangolini, Alessandra ^[1]; Pinton, Paolo ^[2]; Senno, Laura del ^[1]; Aguiari, Gianluca ^[1]

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1. Department of Biomedical and Specialty Surgical Sciences, University of Ferrara, 44121 Ferrara (Italy)
2. Department of Morphology, Surgery and Experimental Medicine, Section of General Pathology, University of Ferrara, 44121 Ferrara (Italy)

Highlights: •Berberine at appropriate doses slows cell proliferation in ADPKD cystic cells. •Reduction of cell growth by berberine occurs by inhibition of ERK and p70-S6 kinase. •Higher doses of berberine cause an overall cytotoxic effect. •Berberine overdose induces apoptotic bodies formation and DNA fragmentation. •Antiproliferative properties of this drug make it a new candidate for ADPKD therapy. -- Abstract: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary monogenic disorder characterized by development and enlargement of kidney cysts that lead to loss of renal function. It is caused by mutations in two genes (PKD1 and PKD2) encoding for polycystin-1 and polycystin-2 proteins which regulate different signals including cAMP, mTOR and EGFR pathways. Abnormal activation of these signals following PC1 or PC2 loss of function causes an increased cell proliferation which is a typical hallmark of this disease. Despite the promising findings obtained in animal models with targeted inhibitors able to reduce cystic cell growth, currently, no specific approved therapy for ADPKD is available. Therefore, the research of new more effective molecules could be crucial for the treatment of this severe pathology. In this regard, we have studied the effect of berberine, an isoquinoline quaternary alkaloid, on cell proliferation and apoptosis in human and mouse ADPKD cystic cell lines. Berberine treatment slows cell proliferation of ADPKD cystic cells in a dose-dependent manner and at high doses (100 μg/mL) it induces cell death in cystic cells as well as in normal kidney tubule cells. However, at 10 μg/mL, berberine reduces cell growth in ADPKD cystic cells only enhancing G{sub 0}/G{sub 1} phase of cell cycle and inhibiting ERK and p70-S6 kinases. Our results indicate that berberine shows a selected antiproliferative activity in cellular models for ADPKD, suggesting that this molecule and similar natural compounds could open new opportunities for the therapy of ADPKD patients.

• OSTI ID: 22242199
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 3 Vol. 441; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
AMP
CELL PROLIFERATION
GROWTH FACTORS
MICE
PHOSPHOTRANSFERASES
RECEPTORS
THERAPY
TUBULES