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Anticarcinoma Activity of Rhodamine 123 against a Murine Renal Adenocarcinoma

Urologic Oncology Research Laboratory, Department of Surgery [H. W. H., R. H., W. D. W. H., W. F. W.], and the Laboratory of Investigative Cytology, Department of Pathology [J. L. H., M. R. M.], Memorial Sloan-Kettering Cancer Center, New York, New York 10021

The mitochondria of carcinoma cells retain the permeant cationic compound rhodamine 123 longer than the mitochondria of normal epithelial cells. The possibility of exploiting this difference in the chemotherapy of a murine renal adenocarcinoma was investigated. Rhodamine 123 exhibited anticarcinoma activity in mice and this activity was potentiated by 2-deoxyglucose and methylglyoxal bis(guanylhydrazone), a chemotherapeutic agent that is toxic to mitochondria. Prolonged retention of rhodamine 123 by renal tumor cells compared with normal renal epithelial cells was demonstrated by flow cytometry, perhaps explaining its antitumor activity. A combination of both mitochondrial toxins, rhodamine 123 and methylglyoxal bis(guanylhydrazone) produced the longest survival and had the greatest antitumor effect.

¹ To whom requests for reprints should be addressed, at Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021.

Received 7/ 2/87. Revised 10/15/87. Accepted 1/ 7/88.