11 September 2015

Anti-cancer drug will become cheaper

Genetic engineering has turned laboratory tobacco into a cure for cancer

Daria Zagorskaya, Vesti 

Throughout their existence, people have relied on plants as a source of medicines. Even modern manufacturers get about half of their drugs from plants. But when this process is hampered by the threat of species extinction or difficulties in cultivation, bioengineering comes into play.

It was among such plants that the nogolist or Podophyllum hexandrum (Podophyllum hexandrum) from the barberry family, which grows in the Himalayas, turned out to be. This plant was the primary source of podophyllotoxin, which formed the basis of the anti-cancer drug etoposide.

Etoposide has been on the medical market since 1983 and is used to treat dozens of types of cancers, including lymphoma and lung cancer. At the moment, the main source of podophyllotoxin for him is a more common type of nogolist – podophyll thyroid, which grows in the eastern part of North America. But this plant also grows slowly and produces less of the necessary toxin than its Asian relative.

Nogolists use podophyllotoxin to protect against pests, and it is consistently synthesized from precursors. But until now, scientists did not know which genes were responsible for this process in order to start and regulate it in the laboratory. It was only known that the substance is not produced constantly.

Finally, chemists from Stanford University managed to make a huge step in the study of the synthesis of podophyllotoxin. Dr. Elizabeth Sattely and her graduate student Warren Lau found out that the toxin in the plant is produced only in response to damage. The authors published a description of their achievements in an article published in the journal Science (Warren Lau, Elizabeth S. Sattel, Six enzymes from mayapple that complete the biosynthetic pathway to the etoposide aglycone).

The researchers made tiny punctures in the healthy leaves of Himalayan nogolist and traced which proteins were synthesized in their cells before and after manipulation. They managed to find 31 new proteins that appeared after the damage and could potentially participate in the sequential assembly of chemical "weapons". As a result, 10 were singled out among them, which completely made up the "assembly line".

Then the genes responsible for the production of these proteins were placed in a model plant for laboratory research – a fast–growing and rather unpretentious tobacco (not smoking, Nicotiana tabacum, but its relative, N.benthamiana - VM), which with great success began to produce the necessary toxin.

Now the main task for researchers is to launch the synthesis of podophyllotoxin in yeast, which can be grown in huge quantities, which will fully meet the medical need for a much-needed medicine. In addition, bioengineers have tools in their hands that will allow them to correct genes, and through them the structure of the final chemical compound, which will make it more effective.

It is also important that if successful, the final price of the drug will significantly decrease, and it will become available to more cancer patients around the world.

In a press release from Stanford (Stanford scientists produce cancer drug from rare plant in lab to benefit human health), Dr. Setteli notes that the method she developed may be suitable not only for nogolists, but also for many other plants that serve as sources of valuable medicines and their precursors.

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11.09.2015
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