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Abstract Title:

Curcumin and Epigallocatechin Gallate Inhibit the Cancer Stem Cell Phenotype via Down-regulation of STAT3-NFκB Signaling.

Abstract Source:

Anticancer Res. 2015 Jan ;35(1):39-46. PMID: 25550533

Abstract Author(s):

Seyung S Chung, Jaydutt V Vadgama

Article Affiliation:

Seyung S Chung

Abstract:

BACKGROUND/AIM: The cancer stem cell (CSC) model postulates the existence of a small proportion of cancer cells capable of sustaining tumor formation, self-renewal and differentiation. Signal Transducer and Activator of Transcription 3 (STAT3) signaling is known to be selectively activated in breast CSC populations. However, it is yet to be determined which molecular mechanisms regulate STAT3 signaling in CSCs and what chemopreventive agents are effective for suppressing CSC growth. The aim of this study was to examine the potential efficacy of curcumin and epigallocatechin gallate (EGCG) against CSC and to uncover the molecular mechanisms of their anticancer effects.

MATERIALS AND METHODS: To suppress the CSC phenotype, two breast cancer cell lines (MDA-MB-231 cells and MCF7 cells transfected with HER2) were treated with curcumin (10μM) with or without EGCG (10 μM) for 48 h. We used tumor-sphere formation and wound-healing assays to determine CSC phenotype. To quantify CSC populations, Fluorescence-activated cell sorting profiling was monitored. STAT3 phosphorylation and interaction with Nuclear Factor-kB (NFkB) were analyzedby performing western blot and immunoprecipitation assays.

RESULTS: Combined curcumin and EGCG treatment reduced the cancer stem-like Cluster of differentiation 44 (CD44)-positive cell population. Western blot and immunoprecipitation analyses revealed that curcumin and EGCG specifically inhibited STAT3 phosphorylation and STAT3-NFkB interaction was retained.

CONCLUSION: This study suggests that curcumin and EGCG function as antitumor agents for suppressing breast CSCs. STAT3 and NFκB signaling pathways could serve as targets for reducing CSCs leading to novel targeted-therapy for treating breast cancer.

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Sayer Ji
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