Root may stem breast cancer spread

EMORY (US) — A compound from roots used in one of the world’s oldest medical systems prevents breast cancer cells from metastasizing in animals.

A new study showing that withaferin A’s anti-metastatic properties could form the basis of drug regimens aimed at preventing cancer recurrence is published online in the International Journal of Cancer.

“Most patients who die from cancer die because of metastases, not from the primary tumor,” says senior author Adam Marcus, assistant professor of hematology and medical oncology at Emory University.

“Our objective was not to find a way to kill cells, but instead, prevent them from migrating and invading other tissues.” The first author of the paper is postdoctoral fellow Jose Thaiparambil.

Withaferin A comes from withania somnifera, also known as ashwagandha, whose roots are used in Ayurvedic medicine that originated in India and has evolved there over thousands of years.

Researchers focused on withaferin A because it is known to bind the protein vimentin that is overproduced in cancer cells, especially those from invasive tumors that are more likely to metastasize.

The team looked for a concentration of withaferin A that prevents migration and invasion in laboratory tests but doesn’t kill cells. Withaferin A appears to prevent vimentin from forming a network within the cell.

In mice, it prevents breast cancer cells from spreading to the lung. Testing a set of chemically modified versions of withaferin A revealed that a particular region of the molecule is important for its anti-invasive activity and ability to disrupt vimentin.

In the 1990s, scientists found that mice lacking vimentin develop normally—a surprising result for a protein that looks like a basic building block of the cell that suggests that clinical use of withaferin A could have minimal toxic side effects.

It may be possible for withaferin A to be taken in low doses over long periods of time to prevent cancer metastasis, either in combination with chemotherapy or after these treatments are completed.

The research is now focusing on whether Withania somnifera contains other compounds that work together with withaferin A, comparing the root extract against purified withaferin A. In addition, other compounds identified independently that bind vimentin might have even more favorable properties, he says.

The work was supported by the Godfrey Charitable Trust, the American Cancer Society, the National Center for Complementary and Alternative Medicine, and Golfers against Cancer.

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