Grape Seeds Natural Cure for Cancer?
After reading Hallmarks of Cancer: The Next Generation, it's apparent that the reversion of cancerous epithelial cells to their mesenchymal state allows cancer stem cells to move throughout the body. This epithelial-to-mesenchymal transition (EMT) is the first step in the metastasis of cancer, with colonization occuring next. There are markers specific to both epithelial cells and mesenchymal cells, which is what Sun and colleagues looked at to determine that GSPs inhibit EMT and, in some cases, even reverse the effects of cancer cells that have already undergone EMT.
Sun and colleagues compared the presence of epithelial and mesenchymal markers before and 48 hours after administering 0, 10, 20, and 40 ul of GSPs to HNSCC cells in vitro. (The researchers experimentally determined the most invasive HNSCC cell type was OSC19 from the tongue and used the cells from this lineage throughout their experiments). Epithelial cells are characterized by the proteins E-cadherin, Keratin 8 & 18, and Desmoglein-2, while mesenchymal cells express N-cadherin, vimentin, fibronectin, and slug. After just 48 hours of being treated with GSPs, researchers found a dose-dependent increase of epithelial cell markers and decrease of mesenchymal cell markers on the cancer cells. Part A of the figure below shows the number of cells with migrating ability stained dark purple. Part B of the same figure is a graphical representation of the same information. It is clear that the higher the dose of GSPs provided, the less able the cells are to transition from epithelial cells to mobile, mesenchymal cells. Stopping cancer cells from undergoing EMT prevents the cells from being able to metastasize, and thus making them deadly.
After further experimentation, Sun and colleagues created the following diagram to depict the mechanism behind the inhibition of EMT by GSPs. Overall, GSPs inhibit the expression of EGFRs (epithelial growth factor receptors), which are found to be overly expressed in 90% of HNSCC cases. GSPs also inhibit the downstream targets of EGFRs, like the protein ERK and the transcription facter NF-kB. The result of 48 hour treatment with GSPs is a reduction in cancer cell invasion via inhibition of epithelial-to-mesenchymal transition, as well as a reversal of cells from the mesenchymal state to the epithelial state. Therefore, even cells that had metastasized would not be able to invade any further. GSPs could potentially be very useful in conjunction with radiation and chemotherapy. The GSPs could stop the cancer in its tracks, while the radiation and chemotherapy could kill, hopefully removing all the cancer cells from the body.
Researchers also tested the effects of Gefitinib and Erlotinib, compounds known to inhibit cancer cell invasion. Although both Gefitinib and Erlotinib reduce EMT, longterm treatment of these compounds can have negative cytotoxic effects. One of the great things about using GSPs to treat cancer is that they are effective and non-toxic. Also, based on other article abstracts, they work on a wide range of different cancers: prostate, breast, colorectal, and skin, to name a few. GSP therapy is so promising there is currently a clinical trial in progress to study the effect of GSPs in conjunction with chemotherapy at reducing and preventing breast cancer cells from forming.
Lastly, I think it is important to remember that the effect of GSPs in vitro is likely different than what it will be in vivo. Sun and colleagues conclude their article by reminding readers that, in order to be effective, proanthocyanidins must reach their target in the human body. Studies show that ingestion of compounds similar to GSPs are not as effective at cancer treatment as in vitro studies, although they are still somewhat effective (~50%). While I have no knowledge as to how GSPs are processed by the digestive system, I anticipate that some of the biggest challenges preventing them from reaching consumers will involve problems in human metabolism and transport.
NOTE: There is a difference between grape seed proanthocyanidins and grape seed oil. During the process to obtain grape seed oil, many ofthe proanthocyanidins are lost, making the extract less effective at inhibiting EMT than GSPs. I came across a news article that professed the ineffectiveness of grape seed oil at curing cancer, and the reason is likely due to the reason above.
