The Effect of Podophyllotoxin on Tissue Metabolism

The crude drug, podophyUin, which is derived from the May-apple root, has been used for many years as a cathartic agent. The carcinoclastic action and effectiveness of this material against condylomata acuminata (venereal warts) have only recently been described. Kaplan (1) and subsequent workers (2-7) produced involution of condylomata acuminata by the local application of a suspension of podophyllin in oil. Culp and Kaplan (3) obtained dramatic results in two hundred cases within 2 to 3 days after a single appfication of podophyUin, and noted little or no effect on surrounding normal tissue. Reich and coworkers (8) reported necrosis and sloughing of soft papillomas of the female urethra after local application of podophyllotoxin, one of the pure constituents of podophyllin, and Tomskey, Vickery, and Getzoff successfully treated granuloma inguinale in twenty patients (9). Ormsbee, Cornman, and Berger (10) observed selective damage of tumor ceils in tissue culture at podophyllin concentrations of 0.08 to 20 rag. per liter, and Belkin (11) found that subcutaneous injection of podophyllin into the mouse caused a marked retardation in the rote of growth of a transplanted tumor (sarcoma 180). The chick embryo is so sensitive to podophyllotoxin that 1 gamma, injected into the yolk sac of the egg, is fatal (12). The changes in the mitotic activity and patterns of squamous epithelia induced by podophyllin (6) suggest a direct and specific effect on the dividing cell. This conclusion is strengthened by the observations that podophyllin blocks mitosis in the root tips of Allium cepa (13), and destroys the mitotic spindles in cleaving Asterlas and Arbacia eggs (14). Despite the unusual biologica] properties and the carcinoclastic action of podophyilotoxin (15), the effects of this interesting compound on enzymes and tissue metabolism have received little attention. Waravdekar and Leiter (16) have reported recently that 10 to 100 rag. of podophyilotoxin per liter in vitro did not significantly affect the respiration of tissue homogenates, but that the subcutaneous injection of 20 rag. per kg.