Mayapple podophyllin

Etoposide and teniposide are semisynthetic podophyllotoxin derivatives (see Table 124-13). Podophyllin is extracted from the mayapple or mandrake plant. Like the vinca alkaloids, podophyllin itself binds to tubulin and interferes with microtubule formation. Unlike the parent compound, however, etoposide and teniposide damage tumor cells by causing strand breakage through inhibiting topoisomerase Resistance may be caused by differences in topoisomerase II levels, by increased cell ability to repair strand breaks, or by increased levels of P-glycoproteins. Etoposide and teniposide are usually clinically cross-resistant. They are cell-cycle phase-specific and arrest cells in... 

The resin product obtained by extraction of the dried roots and rhizomes of the North American plant Podophyllum peltatum L. (the American mandrake or mayapple) and of the related Indian species Podophyllum emodi Wall. Ex Royle is known as podophyllin and has long been known to possess medicinal properties. The major active substance in podophyllin is the lignan lactone podophyllotoxin (7) although a variety of other lignans and lignan glycosides have also been isolated from podophyllin. ... 

The epipodophyllotoxins (Fig. 42.38) are semisynthetic glycosidic derivatives of podophyllotoxin, the major component of the resinous podophyllin isolated from the dried roots of the American mandrake or mayapple plant (Podophyllum peltatum). Although these compounds are capable of binding to tubulin and inhibiting mitosis, their primary mechanism of antineoplastic action is poisioning topoisomerase II, a mechanism that they share... 

Toxicity has been reported after topical and internal administration of products (podophyllin and podophyl-lotoxin) derived from Himalayan mayapple and included nausea, vomiting, peripheral neuropathy, difficulty breathing, lethargy, and coma. Some cases of toxicity have been fatal (Cassidy et al. 1982 McFarland and McFarland 1981). 

Case reports and animal studies have indicated that compounds from Himalayan mayapple have abortifacient activity (Chamberlain et al. 1972 Didcock et al. 1952 Longstaff and von Krogh 2001). A safety assessment of the compounds podophyllotoxin and podophyllin indicated that the topical use of these compounds during pregnancy is strongly contraindicated (Longstaff and von Krogh 2001). 

The LD50 of a fractionated extract (with podophyllin and podophyllotoxin removed) of Himalayan mayapple in mice is 250 mg/kg after oral administration and 90 mg/kg after intraperitoneal administration (Gupta et al. 2008a, 2008b Lata et al. 2009). 

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