Hareesh Nair of the Texas Biomedical Research Institute, and colleagues, write about their findings in the April issue of Molecular Cancer Therapeutics.
In their background information they explain that previous studies have shown gossypin, a flavone originally isolated from the hibiscus plant (H. vitifolius), suppresses inflammation and cancer. However, the underlying molecular activity has not been clear.
In this study, they show that the substance inhibits the action of two gene mutations that commonly occur in people with melanoma, as Nair explains in a press statement:
"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."
According to the American Cancer Society, every year, about 76,000 people are diagnosed with melanoma, the least common form of skin cancer, but the one responsible for the most deaths.
There is currently no single drug or combination that treats all types of melanoma.
For their study, Nair and colleagues tested the effect of gossypin on melanoma in cell cultures and also in live mice.
In the cell culture experiments they found that gossypin stopped cancer cell growth in melanoma cell lines that contained the two gene mutations and stopped the growth of various human melanoma cells.
They suggest gossypin stunted the activity of the mutations by binding with them directly "as confirmed by molecular docking studies".
Gossypin treatment also reduced tumor volume and increased survival rate in mice transplanted with human melanoma tumors containing the two mutated genes.
The authors conclude that:
"In summary, this study identified gossypin as a novel agent with dual inhibitory effects for BRAFV600E kinase and CDK4 for treatment of melanoma."
Nair says the findings "open a new avenue for the generation of a novel class of compounds for the treatment of melanoma".
He and his team now plan to do further studies to understand how the body absorbs and metabolizes gossypin.
The study was funded by the Texas Biomedical Forum and the Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation.
In another recent study, researchers report that Amgen's virus-based melanoma drug TVEC is showing promising early results in a phase 3 trial.
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"Gossypin as a Novel Selective Dual Inhibitor of v-raf Murine Sarcoma Viral Oncogene Homolog B1 and Cyclin-Dependent Kinase 4 for
Melanoma"; Shylesh Bhaskaran, Kalarikkal V. Dileep, Sathyaseelan S. Deepa, Chittalakkottu Sadasivan, Mitch Klausner, Naveen K.
Krishnegowda, Rajeshwar R. Tekmal, John L. VandeBerg, and Hareesh B. Nair; Molecular Cancer Therapeutics April 2013 12:361-372,
first published online 29 Mar 2013; DOI: 10.1158/1535-7163.MCT-12-0965; Link to Abstract.
Additional sources: Texas Biomedical Research Institute.
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