Tumors must induce angiogenesis, the growth of new blood vessels, in order to grow beyond a very small size. In fact, cancer cells start to induce angiogenesis during early stages of tumor development — this is a crucial step that separates preinvasive and dormant forms of cancer from invasive and metastatic growth. Ellagic acid has been shown to inhibit a series of angiogenesis processes in breast cancer cells, including proliferation, migration, and tube formation. Now a new study has reported a mechanism of action by which ellagic acid reduces proliferation of hormone receptor positive (ER+/PR+) breast cancer cells.
Latest research describes mechanism by which ellagic acid inhibits proliferation
The study referenced at the beginning of this news story was designed to investigate the underlying molecular mechanisms by which ellagic acid inhibits MCF-7 (ER+/PR+) breast cancer growth. In particular, the authors sought to determine whether ellagic acid inhibits the proliferation of such cells by altering the regulation of the TGF-β/Smad3 signaling pathway. To conduct the study, MCF-7 breast cancer cells were transfected with pEGFP-C3 or pEGFP-C3/Smad3 plasmids, and treated with ellagic acid alone or in combination with SIS3, a specific inhibitor of Smad3 phosphorylation. The authors assessed the degree of cell proliferation, monitored the cell cycle, and detected gene expression.
SIS3 was shown to reduce the inhibitory activity of ellagic acid on the proliferation of MCF-7 cells. In addition, ellagic acid was found to induce G0/G1 cell cycle arrest (which in turn was mitigated by SIS3). Furthermore, the authors demonstrated that SIS3 reversed the effects of ellagic acid on the expression of downstream targets of the TGF-β/Smad3 pathway. The authors conclude that ellagic acid leads to decreased phosphorylation of RB proteins mainly through modulation of the TGF-β/Smad3 pathway, thereby inhibiting the proliferation of MCF-7 breast cancer cells.
Please see our articles on pomegranates and what ER+/PR+ breast cancer patients and survivors should eat for more information.