Estrogen receptor-α36 is involved in epigallocatechin-3-gallate induced growth inhibition of ER-negative breast cancer stem/progenitor cells

Epigallocatechin-3-gallate (EGCG) is a type of catechin extracted from green tea, which is reported to have anticancer effects. EGCG is also reported to inhibit the cancer stem/progenitor cells in several estrogen receptor (ER)-negative breast cancer cell lines, such as SUM-149, SUM-190 and MDA-MB-231. And all these cancer cells are highly expressed a new variant of ER-alpha, ER-alpha 36. The aim of our present study is to determine the role of ER-alpha 36 in the growth inhibitory activity of EGCG towards ER-negative breast cancer MDA-MB-231 and MDA-MB-436 cells. We found that EGCG potently inhibited the growth of cancer stem/progenitor cells in MDA-MB-231 and MDA-MB-436 cells, and also reduced the expression of ER-alpha 36 in these cells. However, in ER-alpha 36 knocked-down MDA-MB-231 and MDA-MB-436 cells, no significant inhibitory effects of EGCG on cancer stem/progenitor cells were observed. We also found that down-regulation of ER-alpha 36 expression was in accordance with down-regulation of EGFR, which further verified a loop between ER-alpha 36 and EGFR. Thus, our study indicated ER-alpha 36 is involved in EGCG's inhibitory effects on ER-negative breast cancer stem/progenitor cells, which supports future preclinical and clinical evaluation of EGCG as a therapeutic option for ER-alpha 36 positive breast cancer. (C) 2015 Japanese Pharmacological Society. Production and hosting by Elsevier B.V.