The mayapple is Minnesota's native plant and ranges from Quebec to Texas and Florida. Podophyllum peltatum is its Latin name. The plant and its constituents have been in the medical literature for more than 250 years. The folkloric use of mayapple derives from various Native American groups, who used the plant both as medicine and poison. During late 19th century, the Penobscot Indians of Maine used underground parts of the mayapple for the treatment of cancer, and it was also used by physicians in Louisiana and Mississippi for venereal warts.184 Podophyllin, the resin prepared from an alcoholic extract of the rhizomes and roots, was very popular as a cathartic, vermifuge, and emetic. It was produced commercially in the U.S. and exported to Europe. Podophyllin was included in the U.S. Pharmacopoeia as an official drug from 1820 until 1942.

Inspired by mayapple's traditional application and its action against warts, Hartwell and coworkers at the U.S. National Cancer Institute explored its potential as a possible cure in cancer treatment. They identified the correct structure for the major toxin, podophyllotoxin. Podophyllotoxin exhibited anticancer activity in animal studies and human studies, but clinical trials were abandoned when the substance was found to be too toxic. Later, Sandoz Ltd. in Basel, Switzerland, picked up the podophyllotoxin research in the 1960s and developed several new analogs by incorporating subtle changes in the general structure. Two of the semisynthetic analogs, teniposide (VM-26) and etoposide (VP-16), were found to be very active yet relatively safe to human consumption and were approved by the FDA. These two compounds have been widely used to treat non-Hodgkin's lymphomas, leukemias, small-cell lung cancer, and testicular cancer. Teniposide is also being prescribed to treat brain tumors and childhood leukemias. Podophyllin is an example of a product where a new pharmaceutical has been evolved based on a generous lead provided by traditional medicine.

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