Pentagalloylglucose inhibits estrogen receptor alpha by lysosome-dependent depletion and modulates ErbB/PI3K/Akt pathway in human breast cancer MCF-7 cells

Molecular Carcinogenesis
Kuo-Tai HuaJen-Kun Lin

Abstract

Estrogens and estrogen receptors (ER) play important roles in estrogen-dependent and ER-positive breast cancer development. Inhibitors against estrogen biosynthesis or anti-estrogens have been used in breast cancer treatment for many years. The aim of this study was to determine whether pentagalloylglucose (5GG) has inhibitory effects on ER function. In the present study, we found that 5GG significantly reduced the growth of estrogen-responsive human breast cancer MCF-7 cells, and suppressed the phosphorylation and protein level of estrogen receptor alpha (ERalpha). Interestingly, 5GG decreased ERalpha protein levels by promoting the degradation of ERalpha protein in the lysosome. The ERalpha can be activated through a ligand-dependent and/or a ligand-independent pathway. The activated Akt kinase was shown to directly phosphorylate ERalpha at its serine residues and cause ligand independent activation. Our results showed that 5GG might inhibit the phosphatidylinositol 3-kinase (PI3K)/Akt pathway either through directly inhibiting Akt kinase activity or through inhibiting phosphorylation of the upstream receptor tyrosine kinases. The depletion of ErbB family receptors, including epidermal growth factor receptor (EGFR), ErbB2, an...Continue Reading

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Citations

Mar 23, 2011·Reproductive Sciences·Lin-Hung WeiChi-An Chen
Dec 16, 2020·International Journal of Molecular Sciences·Wei-Ting ChangSheng-Nan Wu

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