for those her2+ AND ER+ new drug in development

[Lani]

Not only degrades ER but also inhibits all her family receptors (EGFR, her2, her3 and her4) and its related to a compound found in black tea:

1: Mol Carcinog. 2006 Apr 24; [Epub ahead of print] Related Articles, Links

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

Hua KT, Way TD, Lin JK.

Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.

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, and ErbB3, was also observed. 5GG treatment also led to a dose-dependent decrease in the expression of the estrogen-activated cyclin D1 expression. These findings suggested that 5GG might be a useful chemopreventive or therapeutic agent for hormone-dependent breast cancer through suppressing the functions of ERalpha by lysosome-dependent depletion and modulating the ErbB/PI3K/Akt pathway