The influence of digitonin upon the growth of carcinoma

Abstract

It has been shown by Windaus 1 that digitonin combines with cholesterol to form a very insoluble and pharmacologically inactive compound. In view of the marked influence of cholesterol in accelerating the growth of carcinoma we have thought it of importance to ascertain the influence of digitonin upon the growth of Flexner-Jobling carcinoma in rats.

The digitonin employed was Merck's, stated to have no physiological action upon the heart. By heating the preparation to boiling in m/6 NaCl solution a soapy-looking fine suspension is formed which settles out in the course of several hours. We injected the digitonin, suspended either in m/6 NaCl, or in m/6 NaCl containing 1 per cent. of lecithin, directly into the tumors.

One hundred and sixty-six white rats were inoculated with Flexner-Jobling carcinoma in the axillary region. The number of successful inoculations, determined after 20 days, was 64, or 39 per cent.

On the 20th day after inoculation these animals were sorted, without selection, into three batches, of which one (consisting of 12 animals) served as controls, another (12 animals) received injections of digitonin, and the third (40 animals) received injections of digitonin together with lecithin.

We began by administering I C.C. of a 1 per cent. suspension of digitonin, suspended in m/6 NaCl and in m/6 NaCl + 1 per cent. lecithin respectively. The animals which received digitonin without lecithin evinced symptoms of severe local irritation, and one of the animals which received digitonin alone and two of those which received digitonin and lecithin died within a few hours after the treatment. Post-mortems showed that the heart had in each case stopped in extreme systole, the auricles being engorged. In subsequent treatments the dose of digitonin was reduced to I C.C. of a 0.5 per cent. suspension, and in the case of the animals which received lecithin, the concentration of the lecithin emulsion was increased to 2 per cent.