For the first time, scientists have demonstrated the mechanism of action of gossypin, a naturally-occurring substance found in fruits and vegetables, as a treatment for melanoma, which causes the majority of deaths from skin cancer.
"We identified gossypin as a novel agent with dual inhibitory activity towards two common mutations that are the ideal targets for melanoma treatment," said Texas Biomed's Hareesh Nair, Ph.D.
At the moment, there is no single therapeutic agent or combination regimen available to treat all melanomas, of which about 76,000 new cases are diagnosed annually, according to the American Cancer Society.
"Our results indicate that gossypin may have great therapeutic potential as a dual inhibitor of mutations called BRAFV600E kinase and CDK4, which occur in the vast majority of melanoma patients. They open a new avenue for the generation of a novel class of compounds for the treatment of melanoma," Nair added.
His report, appearing in the March 29, 2013 issue of the journal Molecular Cancer Therapeutics, was funded by the Texas Biomedical Forum and the Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation.
Nair and his colleagues found that gossypin inhibited human melanoma cell proliferation, in vitro, in melanoma cell lines that harbor the two mutations. Gossypin stunted activities of the mutated genes, possibly through direct binding with them. It also inhibited the growth of various human melanoma cells. In addition, gossypin treatment for 10 days of human melanoma cell tumors with the mutations transplanted into mice reduced tumor volume and increased survival rate.
Further studies are planned by Nair's team to understand how the body absorbs gossypin and how it is metabolized. This idea has been discussed with the Cancer Therapy & Research Center at the UT Health Science Center San Antonio's Deva Mahalingam, M.D, Ph.D., who is interested in testing gossypin in melanoma patients.
Co-authors on the paper include John L. VandeBerg, Ph.D., and Shylesh Bhaskaran, Ph.D., of Texas Biomed; Kalarikkal V. Dileep, M.Sc., and Chittalakkottu Sadasivan, Ph.D., of Kannur University, in Palayad, India; Deepa S. Sathyaseelan, Ph.D., of the Barshop Institute for Longevity and Aging Studies at the UT Health Science Center San Antonio; Mitch Klausner, Ph.D., of the MatTek Corporation; and Naveen K. Krishnegowda, M.D., and Rajeshwar R. Tekmal, Ph.D., of the Department of Obstetrics and Gynecology at the UT Health Science Center San Antonio.
Texas Biomed, formerly the Southwest Foundation for Biomedical Research, is one of the world's leading independent biomedical research institutions dedicated to advancing health worldwide through innovative biomedical research. Located on a 200-acre campus on the northwest side of San Antonio, Texas Biomed partners with hundreds of researchers and institutions around the world, targeting advances in the fight against AIDS, hepatitis, malaria, parasitic infections and a host of other infectious diseases, as well as cardiovascular disease, diabetes, obesity, cancer, psychiatric disorders, and problems of pregnancy. For more information on Texas Biomed, go to http://www.TxBiomed.org, or call Joe Carey, Texas Biomed's Vice President for Public Affairs, at 210-258-9437.
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