Plant Cell Cultures As Producers Of Secondary Metabolites: Podophyllum Lignans As A Model

Podophyllums have been used extensively as medicinal plants and are part of the folklore in Asian and American cultures. Their use dates back to the Chinese culture of 2,000 years ago where they were used as an antitumor drug. The resin podophyllin was first recommended as an antiviral agent and provided clues for new applications. The most important secondary metabolite isolated from the rhizomes and roots of the Podophyllum species is podophyllotoxin and its related lignans. This lignan is the precursor of the semisynthetic drugs etoposide, teniposide, and etopophos, which are clinically used in the therapeutic treatment of cancer. Moreover, other derivatives have shown different types of biological activity. With an increasing worldwide market for anticancer drugs, supplies of podophyllotoxin for the pharmaceutical industry are under great pressure. As the chemical synthesis of podophyllotoxin is not economic on a commercial scale, supplies are still obtained from wild populations of Podophyllum. Concern has been expressed about the shortage of Podophyllum which is now an endangered species due to overexploitation and a lack of cultivation. Attempts to increase plant yields have improved through in vitro technology while the production of podophyllotoxin will require further studies. This chapter provides an overview of the Podophyllum species and its lignans. Podophyllum biotechnology still presents challenges to be overcome and some of these are, in part, discussed in this chapter.