Curcumin inhibits renal cyst formation and enlargement in vitro by regulating intracellular signaling pathways

Abstract

Autosomal dominant polycystic kidney disease, a common inherited disease affecting about 1/1000 and 1/400 live births, is characterized by massive enlargement of fluid-filled cysts and eventually causes renal failure. The purpose of this study is to identify the inhibitory effect of curcumin on renal cyst development and to investigate the inhibitory mechanism. Madin-Darby canine kidney (MDCK) cyst model and murine embryonic kidney cyst model were used to evaluate inhibitory activity. Cell viability, proliferation, apoptosis, CFTR function and expression, and signaling pathways in MDCK cells were determined to explore the mechanism of cyst inhibition. Curcumin was found to significantly inhibit MDCK cyst development. At maximum dose curcumin caused 62% inhibition of the cyst formation (IC(50) was 0.12 μM). Curcumin slowed cyst enlargement in both MDCK cyst model and embryonic kidney cyst model with dose-response relationship. Curcumin neither induced cytotoxicity nor apoptosis in MDCK cells at <100 μM. Curcumin failed to affect the chloride transporter CFTR expression and function. Interestingly, curcumin inhibited forskolin-promoted cell proliferation and promoted the tubule formation in MDCK cells, which indicates curcumin promotes MDCK cell differentiation. Furthermore, curcumin reduced the intracellular signaling proteins Ras, B-raf, p-MEK, p-ERK, c-fos, Egr-1, but increased Raf-1 and NAB2 in MDCK cells exposed to forskolin. These results define that curcumin inhibits renal cyst formation and enlargement and suggest that curcumin might be developed as a candidate drug for polycystic kidney disease.