Researchers at the University of Kentucky have advanced research of a natural product found in an Indian medicinal plant that has shown effectiveness in blocking blood-vessel and tumor growth. The discovery may help lead to treatments for certain types of metastatic breast, prostate and colon cancers.
Royce Mohan, assistant professor of ophthalmology and principal scientist leading this study, reports isolating vimentin, an intermediate filament protein, as the binding target of withaferin-A. The findings are in the June 22 issue of Chemistry & Biology.
The lead author in this study, ophthalmology assistant professor Paola Bargagna-Mohan, utilizing a chemical analog of withaferin-A (synthesized in collaborator pharmaceutical sciences assistant professor Kyung Bo Kim’s lab), shows that the drug-like activity of withaferin-A results from binding to and destroying this filament protein. This cytoskeleton targeting activity shuts down the ability of blood vessel cells to grow and migrate, a mechanism which also appears to be relevant to how withaferin-A can block tumor cells from spreading.
Furthering this discovery in developing new classes of drugs from withaferin-A, Adel Hamza, a postdoctoral candidate in pharmaceutical sciences associate professor Chang-Guo Zhan’s lab, has developed a molecular model that reveals the specific binding interaction of withaferin-A with vimentin.
This discovery also signals possible new methods of identifying a number of cancers early in their development, when tumors produce vimentin to enable them to invade tissues and spread to different organs.
The researchers hope certain aspects of their findings will lead to therapeutic developments for individualized medicine due to the well known disease involvement of vimentin.
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