(-)-Epigallocatechin-3-gallate inhibits bladder cancer stem cells via suppression of sonic hedgehog pathway

Cancer stem cells (CSCs) are associated with the occurrence and metastasis of human malignant tumors, and targeting CSCs is an important strategy for cancer prevention and overcoming drug resistance. (-)-Epigallocatechin-3-gallate (EGCG), a bioactive polyphenol from green tea, has been studied extensively for its beneficial effects on various tumors including bladder cancer. However, the mechanism underlying the effect of EGCG on bladder CSCs remains poorly understood. Here, the authors investigated the expression of bladder CSCs markers including cluster of differentiation (CD)44, CD133, Oct4, ALDH1A1 and Nanog, and their role in the effect of EGCG on bladder CSCs. EGCG inhibited bladder cancer tumorspheres, downregulated stem cell markers, suppressed the expression of proliferation-associated proteins in and promoted the apoptosis of bladder CSCs. The effect of EGCG was mediated by the sonic hedgehog signaling pathway, and upregulation of sonic hedgehog signaling pathway components attenuated the suppressive effects of EGCG. Taken together, the results indicated that EGCG could be an important natural compound against bladder CSCs and provide new insights into the effective molecular targeting of bladder CSCs.