Steviol retards cyst growth through inhibition of ERK and wnt/β‐catenin pathways

Abstract

Cystogenesis in polycystic kidney disease (PKD) involves multiple pathways. One of them is cAMP‐stimulated epithelial cell proliferation and cyst enlargement. Previously, we found that steviol could inhibit cyst enlargement in part by inhibition of CFTR function. The present study was aimed to investigate the detailed mechanisms of steviol on cyst growth using Madin Darby canine kidney (MDCK) cyst models. We found that steviol (100 μM) reversibly inhibited MDCK cyst growth by 38.3%. Steviol at the dose up to 200 μM had no cytotoxicity on MDCK cells. Western blot analysis of cysts extracted from collagen demonstrated that steviol reduced ERK 1/2 phosphorylation. In addition, treatment with 100 μM of steviol for 24 h significantly abolished ß‐catenin protein expression in MDCK cells by 33.6%. These findings suggest that steviol retards MDCK cyst enlargement, in part, by retarding cell proliferation through inhibition of ERK signaling and wnt/ß‐catenin pathways. Thus, steviol represents a promising natural plant‐based drug candidate for polycystic kidney disease due to its multiple targets.This work was supported by the Thailand Research Fund, the Office of the Higher Education Commission and Mahidol University under the National Research Universities Initiative and Faculty of Science, Mahidol University, Thailand.