In searching for a new approach to the systemic treatment of
colorectal carcinoma, we have observed that certain lipophilic cationic compounds are accumulated and retained for a significantly longer period in the mitochondria of living
carcinoma cells than in normal cells or
sarcoma cells. We report the in vivo
therapeutic effect of one of these compounds,
dequalinium chloride, on the W163 rat colon
carcinoma isograft, which grows rapidly in Wistar/Furth rats after primary
tumor implantation, and which recurs rapidly after primary
tumor resection. In the primary transplant model,
tumors were implanted, and daily
dequalinium chloride treatments were begun the following day in doses ranging from 1 to 10 mg/kg. In the recurrence model, isografts were implanted, allowed to grow for one week, and then all gross
tumor was resected.
Dequalinium chloride was administered in varying daily doses starting the day after resection. In both models,
tumor was removed on day 11 after implantation or resection. At sublethal doses,
dequalinium chloride significantly inhibited primary
tumor growth to 60% that of controls and recurrent
tumor growth to 50% that of controls. We propose that this unique
biologic approach of targeting
carcinoma mitochondria with lipophilic cationic compounds may provide a major new opportunity for treating
colorectal carcinoma.