Epigallocatechin-3-Gallate Prevents the Acquisition of a Cancer Stem Cell Phenotype in Ovarian Cancer Tumorspheres through the Inhibition of Src/JAK/STAT3 Signaling

Abstract

Three-dimensional tumorsphere cultures recapitulate the expression of several cancer stem cell (CSC) biomarkers and represent an effective in vitro platform to screen the anti-CSC properties of drugs. Whereas ovarian carcinoma is among the leading causes of death for women, ovarian CSC (OvCSC), a highly malignant subpopulation of ovarian cancer cells, is thought to be responsible for therapy resistance, metastasis, and tumor relapse. Epigallocatechin-3-gallate (EGCG), a diet-derived active polyphenol found in green tea leaves, can suppress ovarian cancer cell proliferation and induce apoptosis. However, its capacity to prevent the acquisition of cancer stemness traits in ovarian malignancies remains unclear. Here, we exploited the in vitro three-dimensional tumorsphere culture model to explore the capacity of EGCG to alter CSC biomarkers expression, signal transducing events and cell chemotaxis. Total RNA and protein lysates were isolated from human ES-2 ovarian cancer cell tumorspheres for gene assessment by RT-qPCR and protein expression by immunoblot. Real-time cell chemotaxis was assessed with xCELLigence. Compared with their parental adherent cells, tumorspheres expressed increased levels of the CSC markers NANOG, SOX2, PROM1, and Fibronectin. EGCG treatment reduced dose-dependently tumorspheres size and inhibited the transcriptional regulation of those genes. Src and JAK/STAT3 signaling pathways appeared to be relevant for CSC phenotype and chemotactic response. In conclusion, these data highlight and support the chemopreventive benefits of the diet-derived EGCG and its capacity to target intracellular transducing events that regulate the acquisition of an invasive CSC phenotype.

Exploring the Apoptotic-Induced Biochemical Mechanism of Traditional Thai Herb (Kerra™) Extract in HCT116 Cells Using a Label-Free Proteomics Approach

“…For example, Curcumin, a compound found in rhizomes of Curcuma longa (turmeric), has been shown to have antiproliferative and proapoptotic effects on various cancer cells including colon cancers, prostate cancers, and lung cancers [ 1 , 2 , 3 ]. Epigallocatechin gallate, a compound found in green tea, has been shown to inhibit the growth of various types of cancer cells such as ovarian cancers and head and neck cancer [ 4 , 5 ]. Interestingly, a combination of Curcumin and epigallocatechin gallate exhibited potential anti-cancer activity by inducing apoptosis in various cancers [ 6 ].…”