Premium
Genistein reduced invasive activity of human MCF‐7 and MDA‐MB 231 breast carcinoma cells through decreased tight junction permeability and regulation of related tight junction proteins
Author(s) -
Kim Sung Ok,
Lee Insong James,
Kim MeeKyung,
Choe Won Kyung,
Choi Yung Hyun
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1062.2
Subject(s) - genistein , claudin , tight junction , paracellular transport , mcf 7 , cancer research , metastasis , chemistry , cancer cell , microbiology and biotechnology , cancer , biology , medicine , permeability (electromagnetism) , endocrinology , biochemistry , human breast , membrane
We investigated whether overexpressed claudin‐3 and ‐4, a component of tight junctions (TJs), repressed invasion activity in MCF‐7 and MDA‐MB 231, when treated with genistein. Genistein inhibited the cancer cell growth and tightened TJs in these cells as demonstrated increase in transepithelial electrical resistance and decreased in paracellular permeability of mannitol. The activities of MMP‐2 and ‐9 in cancer cells were decreased by treatment with genistein and occurred in a time dependent manner. Those of MMP‐2 were observed strong compared with those of MMP‐9 in both cell lines and activities and protein levels of MMP‐2 in MDA‐MB 231 were higher than those of MCF‐7. Concurrently, genistein repressed the levels of claudin‐3 and ‐4 proteins and also decreased metastasis related gene expressions, such as IGF‐l and snail and, reversely, increased that of TSP‐1 and E‐cadherin in cancer cells. The inhibitory effect of genistein on invasive activity was functionally confirmed, since it significantly reduced the invasion properties of cancer cells in invasion assay. And also we validated with using claudin‐3 siRNA on invasion activity of breast cancer calls. The demonstration of ability of genistein to tighten TJs and repression of claudin‐3 and ‐4 protein levels points to a novel mechanism by which genistein and possibly other phytochemicals may prevent cancer and metastasis.