Epithelial-mesenchymal transition (EMT) plays a key role in
tumor progression. The cells undergoing EMT upregulate the expression of cell motility-related
proteins and show enhanced migration and invasion. The hallmarks of EMT in
cancer cells include changed cell morphology and increased metastatic capabilities in cell migration and invasion. Therefore, prevention of EMT is an important tool for the inhibition of
tumor metastasis. A novel preventive
therapy is needed, such as treatment of natural dietary substances that are nontoxic to normal human cells, but effective in inhibiting
cancer cells.
Phytoestrogens, such as
genistein,
resveratrol,
kaempferol and
3,3'-diindolylmethane (DIM), can be raised as possible candidates. They are plant-derived dietary
estrogens, which are found in
tea, vegetables and fruits, and are known to have various
biological efficacies, including chemopreventive activity against
cancers. Specifically, these
phytoestrogens may induce not only anti-proliferation, apoptosis and cell cycle arrest, but also anti-
metastasis by inhibiting the EMT process in various
cancer cells. There have been several signaling pathways found to be associated with the induction of the EMT process in
cancer cells.
Phytoestrogens were demonstrated to have chemopreventive effects on
cancer metastasis by inhibiting EMT-associated pathways, such as Notch-1 and
TGF-beta signaling. As a result,
phytoestrogens can inhibit or reverse the EMT process by upregulating the expression of epithelial phenotypes, including
E-cadherin, and downregulating the expression of mesenchymal phenotypes, including
N-cadherin, Snail, Slug, and
vimentin. In this review, we focused on the important roles of
phytoestrogens in inhibiting EMT in many types of
cancer and suggested
phytoestrogens as prominent alternative compounds to
chemotherapy.