Re-purposed Malaysian folk medication reduces resistance to chemotherapy

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Washington, June 28 : A re-purposed Malaysian folk medication has the potential to reduce resistance to chemotherapy agents used to treat cancer, said researchers from McGill University's Faculty of Medicine.

Led by Dr. Jerry Pelletier, of the Department of Biochemistry and the McGill Cancer Centre, an international team of scientists conducted an extensive study on a class of natural products known as cyclopenta benzofuran flavaglines (CBF).

Using, genetically engineered mice to mimic human leukemias, they discovered that one particular CBF compound, silvestrol, can effectively re-sensitize tumors to chemotherapy, making them susceptible to the killing effects of anticancer drugs.

"One of the major problems with cancer therapy is that the tumours either fail to respond or stop responding over time to various chemotherapy drugs. One reasonable explanation for why this happens is the normal process of protein synthesis in the cell is usurped, principally because cancer cells grow faster and have higher metabolic needs. The normal checks and balances are no longer present," said Pelletier.

Focussing on high-throughput assays of various compounds to determine their anti-cancer effectiveness, the researchers found that silvestrol was one compound that showed promise. It is a natural compound derived from Aglaia silvestris, a large genus of trees and shrubs found in Malaysia, South China and some Pacific islands. It has been used in Malaysian folk medicine for generations, but never as a cancer therapy.

"We made a conscious decision early on in our research to also screen for natural products. Silvestrol is not a synthetic compound you can buy from commercial suppliers," said Pelletier.

While working in lab, silvestrol therapy re-sensitized leukemia cells which had already demonstrated resistance to the chemotherapy agent doxorubicin.

"Essentially, we have turned off the cancer cell's survival signals, which is associated with resistance," he said.

But he warned that synthetic silvestrol is now starting to become available, trials in humans and possible treatments are still many years away.

The results of this study were published in the latest issue of The Journal of Clinical Investigation (JCI).

ANI

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