Open AccessBreast cancer cell growth inhibition by phenethyl isothiocyanate is associated with down‐regulation of oestrogen receptor‐α36
Author(s) -
Kang Lianguo,
Wang ZhaoYi
Publication year - 2010
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2009.00877.x
Subject(s) - phenethyl isothiocyanate , cancer research , isothiocyanate , cell growth , cancer , mapk/erk pathway , signal transduction , breast cancer , carcinogenesis , estrogen receptor , cancer cell , chemistry , kinase , medicine , endocrinology , biology , biochemistry
The dietary isothiocyanates (ITCs) exhibit strong chemopreventive activities for a variety of neoplasms including breast cancer. However, the molecular mechanisms underlying ITC function in breast cancer cells have not been well established. Here, we found that phenethyl isothiocyanate (PEITC) acted more potently than the ‘pure’ anti‐oestrogen ICI 182,780 to inhibit the growth of oestrogen receptor (ER) + breast cancer MCF7 and H3396 cells and ER – MDA‐MB‐231 and SK‐BR‐3 cells. PEITC reduced the steady state levels of ER‐α and its novel variant, ER‐α36 in a dose‐and time‐dependent manner and inhibited oestrogen‐induced activation of the mitogen activated protein kinase/ERK 1/2 signaling pathway. However, ICI 182,780 that is potent in destabilization of ER‐α protein, failed to down‐regulate ER‐α36. Our results thus demonstrated that PEITC functions as a more potent ER‐α‘disruptor’ than the well‐known ICI 182,780 to abrogate ER‐mediated mitogenic oestrogen signaling in breast cancer cells, which provides a molecular explanation for the strong growth inhibitory activity of ITCs in breast cancer cells, and a rational for further exploration of ITCs as chemopreventive agents for human mammary carcinogenesis.