Abstract
The beneficial effects of tea consumption on cancer prevention have been generally reported, while (−)-Epigallocatechin-3-gallate (EGCG) is the major active component from green tea. Cancer stem cells (CSCs) play a crucial role in the process of cancer development. Targeting CSCs may be an effective way for cancer intervention. However, the effects of EGCG on colorectal CSCs and the underlying mechanisms remain unclear. Spheroid formation assay was used to enrich colorectal CSCs from colorectal cancer cell lines. Immunoblotting analysis and quantitative real-time polymerase chain reaction were used to measure the alterations of critical molecules expression. Immunofluorescence staining analysis was also used to determine the expression of CD133. We revealed that EGCG inhibited the spheroid formation capability of colorectal cancer cells as well as the expression of colorectal CSC markers, along with suppression of cell proliferation and induction of apoptosis. Moreover, we illustrated that EGCG downregulated the activation of Wnt/β-catenin pathway, while upregulation of Wnt/β-catenin diminished the inhibitory effects of EGCG on colorectal CSCs. Taken together, this study suggested that EGCG could be an effective natural compound targeting colorectal CSCs through suppression of Wnt/β-catenin pathway, and thus may be a promising agent for colorectal cancer intervention.
Highlights
Colorectal cancer is the third most common cancer and the most common gastrointestinal cancer in the world
CD133, ALDHA1, Oct-4, and Nanog were reported evidence has revealed that CD44, spheroids formed in serum-free medium (SFM)
PCR analysis showed that the mRNA levels of the pivotal cancer stem cells (CSCs) markers were upregulated in lines (Figure 2C). These results suggested the characteristics of colorectal CSCs in DLD-1 and SW480 both cell lines (Figure 2C). These results suggested the characteristics of colorectal CSCs in DLD-1 sphere-forming cells cultured in and SW480 sphere-forming cells cultured in SFM
Summary
Colorectal cancer is the third most common cancer and the most common gastrointestinal cancer in the world. More than 1 million people will develop colorectal cancer every year [1]. Despite the advancement of major therapeutic strategies including surgery and chemotherapy, the main causes of death are metastasis and recurrence [2]. Accumulating evidence has demonstrated the existence of cancer stem cells (CSCs) in various solid cancer including colorectal cancer [3]. CSCs are a rare subpopulation of cancer cells that exhibit the abilities of self-renewal and multipotent differentiation. CSCs play a key role in tumor initiation and development. CSCs are crucial for metastasis, drug resistance, as well as recurrence of malignancies [3,4,5,6].
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