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American Mayapple Yields Anti-Cancer Extract / July 17, 2000 / News from the USDA Agricultural Research Service

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When the mayapple is under attack, it turns on defenses that activate potent toxins such as podophyllotoxins.

American Mayapple Yields Anti-Cancer Extract

By Hank Becker
July 17, 2000

WASHINGTON, July 17, 2000--A common weed called mayapple may offer an alternative to an Asian plant that's been harvested almost to extinction for an anti-cancer extract, Agricultural Research Service administrator Floyd Horn announced today.

"Besides providing a dependable, long-term supply of the anti-cancer drug, the new extraction method--if adopted--could turn the American mayapple into a new alternative crop for U.S. growers," Horn said. ARS and University of Mississippi scientists developed the new extraction method.

The near-extinct Asian plant, Podophyllyum emodi, is a cousin of the mayapple weed found in the United States. The Asian plant makes a compound called podophyllotoxin, used in manufacturing the cancer drug etoposide, the active ingredient in a drug used for treating lung and testicular cancer. In chemotherapy, the drug has been shown to inhibit the activity of an enzyme essential for the replication of cancer cells, preventing their spread.

But shrinking supplies of the P. emodi plant in India have resulted in export restrictions. Since synthesis of etoposide from simple building blocks requires a costly multi step process, many attempts have been made to develop alternative natural sources of this compound.

Working with University of Mississippi researchers, plant physiologists Camilo Canel and Frank Dayan with the ARS Natural Products Utilization Research Unit at Oxford, Miss., discovered and developed the new method of extracting podophyllotoxin. With it, they've shown that leaves of the mayapple, P. peltatum, can yield a readily available, plentiful and renewable source of stored podophyllotoxins.

Given the acute toxicity of podophyllotoxin, the scientists think that both species produce the compound as a form of protection from insects and other herbivores.

The ARS-Mississippi team found an efficient way to extract the compound, which the mayapple stores in the form of glucosides. The plant adds a glucose molecule to podophyllotoxins so the compound can be safely stored until the plant is attacked. The key to their extraction is removing podophyllotoxin's "safety-seal."

The new extraction method is fast, efficient and inexpensive. The use of mayapple leaves constitutes a sustainable procedure for providing a dependable, long- term supply of podophyllotoxin.

The team has filled a joint patent on the new technology. Talks are in progress with pharmaceutical firms to license it to make this drug more available in the marketplace.

For more details, see the July issue of Agricultural Research.

ARS is the chief research agency of the U.S. Department of Agriculture.

Scientific contact: Camilo Canel, ARS Natural Products Utilization Research Unit, Oxford, Miss.; phone (662) 915-7965, fax (662) 915-1035, ccanel@oldmiss.edu.

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