Pomegranate extract inhibits EMT in clear cell renal cell carcinoma

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma (RCC) and is characterized by biallelic inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene.

The purpose of this study was to determine the biochemical effects of pomegranate juice extracts on RCC cell lines.

Asian Journal of UrologyRESEARCH TITLE: Pomegranate extract inhibits EMT in clear cell renal cell carcinoma in a NF-κB and JNK dependent manner

COUNTRIES: USA; China

CONDUCTED BY:  Department of Medicine, Division of Hematology-OncologyLos Angeles, USA; Technical Institute of Physics and Chemistry, Chinese Academy of Science, Beijing, China;  Department of Urology, David Geffen School of Medicine at UCLA, Los Angeles, USA; Department of Medicine, Division of Hematology-Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.

PUBLISHED ON: Asian Journal of Urology

RESEACH:

Abstract

Objective

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma (RCC) and is characterized by biallelic inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene. One effect of VHL inactivation is hypoxia inducible factor alpha (HIFα)-independent constitutive activation of nuclear factor kappa B (NF-κB) and c-jun N-terminal kinase (JNK). Both NF-κB and JNK drive ccRCC growth and epithelial to mesenchymal transition (EMT). The purpose of this study was to determine the biochemical effects of pomegranate juice extracts on RCC cell lines.

Methods

The pre-clinical effects of pomegranate juice extracts on NF-κB, JNK, and the EMT phenotype were assayed, including its effect on proliferation, anchorage-independent growth, and invasion of pVHL-deficient RCCs.

Results

PE inhibits the NF-κB and JNK pathways and consequently inhibits the EMT phenotype of pVHL-deficient ccRCCs. The effects of PE are concentration-dependent and affect not only biochemical markers of EMT (i.e., cadherin expression) but also functional manifestations of EMT, such as invasion. These effects are manifested within days of exposure to pomegranate juice extracts when diluted 2000-fold. Highly dilute concentrations of pomegranate juice extracts (106dilution), which do not impact these pathways in the short term, were found to have NF-κB and JNK inhibitory effects and ability to reverse the EMT phenotype following prolonged exposure.

Conclusion

These findings suggest that pomegranate juice extracts may mediate inhibition growth of pVHL-deficient ccRCCs and raises the possibility of its use as a dietary adjunct to managing patients with active surveillance for small, localized, incidentally identified renal tumors so as to avoid more invasive procedures such as nephrectomy.

YEAR: 2015