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Publication Date

11-20-2015

Keywords

curcumin, dietary polyphenol, apoptosis, renal carcinoma

Abstract

Background: Malignant clear cell renal carcinoma (ccRCC) is an aggressive tumor that is highly resistant to chemotherapy and radiation. Current therapeutic approaches to management of ccRCC have not significantly improved patient survival, therefore novel therapies are needed. The von Hippel-Lindau tumor suppressor gene is frequently mutated in ccRCC resulting in unregulated transcriptional activity of hypoxia-inducible factors (HIF) 1α and 2α. HIF-mediated transcription leads to increased growth factor expression and growth factor receptor (GFR)-mediated signaling. NFκB and STAT3 are phosphorylated in response to GFR activation and modulate gene expression, which promotes cell growth and invasion. Activated NFκB and STAT3 expression is associated with ccRCC pathogenesis.

Purpose: 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. To examine the mechanism by which curcumin induced cell death, we used 769-p cells, a highly aggressive human ccRCC cell line that does not express functional von Hippel-Lindau protein. The impact of curcumin on the phosphorylation status and transcriptional activity of NFκB and STAT3, in 769-p cells, was determined.

Results: Our results show that in ccRCC cells curcumin decreased cell proliferation and cell viability, abolished clonogenic property, induced apoptosis and blocked cellular migration. The growth suppressive and proapoptotic effects of curcumin were accompanied by decreased phosphorylation and transcriptional activity of NFκB and STAT3.

Conclusion: The ability of curcumin to induce apoptosis and inhibit migration of ccRCC cells justifies additional studies that explore the potential of developing curcumin or other NFκB and STAT3 inhibitors as novel therapeutic agents in the management of ccRCC.

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