title: Berberine slows cell growth in autosomal dominant polycystic kidney disease cells.
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 G0/G1 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.
authors.affiliation: Department of Biomedical and Specialty Surgical Sciences, University of Ferrara, 44121 Ferrara, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Bonon
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mangolini
authors.forename: Paolo
authors.initials: P
authors.lastname: Pinton
authors.forename: Laura
authors.initials: L
authors.lastname: Del Senno
authors.forename: Gianluca
authors.initials: G
authors.lastname: Aguiari
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001599:Berberine / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects; D051379:Mice; D016891:Polycystic Kidney, Autosomal Dominant / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D050396:TRPP Cation Channels / Q000235:genetics
chemical_list: D001599:Berberine; D048049:Extracellular Signal-Regulated MAP Kinases; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D050396:TRPP Cation Channels
keywords: ADPKD; Apoptosis; Berberine; Cell proliferation; EGFR; ERK; ERK and p70-S6 signaling; cAMP; cyclic adenosine monophosphate; epidermal growth factor receptor; extracellular-signal-regulated kinases; mTOR; mammalian target of rapamycin