Tea bioactive compounds inhibit prostate cancer stem cells via downregulation of Bmi1

Abstract

Cancer stem cells (CSCs) are suggested to be responsible for tumor initiation, progression, drug resistance, recurrence and metastasis. Strategies that target CSCs may significantly prevent and/or delay cancer progression. The objective of this study was to evaluate the effect of tea bioactive components on targeting prostate CSCs. The effect of tea components on the self‐renewal ability of CSCs was evaluated by sphere‐forming efficiency (SFE) assay, gene expression was quantified by real time PCR, and Bmi1 gene silencing was manipulated by siRNA. The SFEs of LNCaP, DUCaP, PC3 and DU145 human prostate cancer cell lines were 2.8%, 15.7%, 1%, and 5.6%, respectively. The expression of several CSC related biomarkers, such as c‐met, Bmi1 and CD44 were increased, whereas the expression of androgen receptor (AR) was decreased in prostate spheres. Tea compounds, especially epigallocatechin gallate and theaflavines inhibited dose‐dependently the SFEs of prostate cancer cells and downregulated the expression of Bmi1 gene. Gene function assay showed that silencing of Bmi1 dramatically inhibited the growth and decreased the sphere‐forming ability of prostate cancer cells. The results derived from our preliminary studies suggest that Bmi1 may play an important role in self‐renewal ability of prostate CSCs, and that tea bioactive components may have inhibitory effect on prostate CSC self‐renewal in part via downregulation of Bmi1 gene expression and function. Supported in part by R21 CA153355 from NCI/NIH