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Publication Date

11-20-2015

Keywords

curcumin, dietary polyphenol, apoptosis, renal carcinoma

Abstract

Purpose

Malignant clear cell renal carcinoma (ccRCC) is an aggressive tumor highly resistant to chemotherapy and radiation. Current therapeutic approaches to management of ccRCC have not significantly improved patient survival, therefore novel therapies are needed. Activated NFκB and STAT3 expression is associated with ccRCC pathogenesis. The dietary polyphenol curcumin is a well-documented antitumor agent and a known inhibitor of NFκB and STAT3 activation. Given the lack of effective therapies that block ccRCC progression, our objective was to examine whether curcumin could suppress the growth and migration of ccRCC cells, and whether this suppression was mediated via inhibition of NFκB and STAT3 activity.

Methods

Human ccRCC cell lines (769-p, 786-o, Caki-1, ACHN and A-498 cells) were exposed to curcumin to assess the impact of curcumin on ccRCC cell viability. Colony formation assay was used to assess the effect of curcumin on ccRCC cell renewal capability. Effect of curcumin on apoptosis was determined by annexin V binding and mitochondrial membrane depolarization assays. The anti-migratory effect of curcumin on ccRCC cells was assessed using the wound healing assay. Effect of curcumin on NFκB and STAT3 phosphorylation in 769-p cells was determined by western blot analysis.

Results

In ccRCC cells, curcumin decreased cell proliferation and cell viability, abolished clonogenic property, induced apoptosis and blocked cellular migration. The growth suppressive and pro-apoptotic effects of curcumin were accompanied by decreased phosphorylation of NFκB and STAT3.

Conclusions

The ability of curcumin to induce apoptosis and inhibit migration of ccRCC cells justifies additional mechanistic and preclinical studies that examine the effect of curcumin or other NFκB and STAT3 inhibitors as potential suppressors of ccRCC tumorigenesis.

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