Activity of MKT 077, a rhodacyanine dye, against human tumor colony-forming units

MKT 077 is related to rhodamine 123 dye and demonstrates preferential accumulation in the mitochondria of cancer cells compared to normal cells. This difference in retention between cancer and normal cells led to the finding that MKT 077 selectively inhibits the growth of cancer cells in vitro, To define the preclinical activity profile of MKT 077, the compound was tested in vivo against a large variety of human tumors utilizing the human tumor-cloning assay. MKT 077 was studied using a sequential 2 h exposure separated by 24 h (2-24-2 h) and a 24 h exposure at final concentrations of 0.1, 0.2, 1.0, 2.0, 10.0 and 20.0 mu g/ml. MKT 077 was also studied using continuous exposure at final concentrations of 0.1, 1.0 and 10 mu g/ml. A decrease in tumor colony formation was considered significant if survival of colonies treated with MKT 077 was 50% or less compared to untreated controls. A total of 149 specimens was treated with MKT 077 with 51, 58 and 34 evaluable specimens with the 2-24-2 h, the 24 h and the continuous exposure, respectively. The results of the present study suggest a positive relationship between concentration and response. No relationship between exposure schedule and activity was observed. Inhibitory effects were obtained against multiple tumor types. High cytotoxic activity was obtained against breast, ovary, endometrial, colon and non-small cell lung cancer with concentrations of 2 mu g/ml or above. In conclusion, the broad spectrum of cytotoxicity of MKT On in the human tumor-cloning assay and the unique mechanism of action of MKT 077 encourage additional preclinical and clinical studies with this compound and other rhodacyanine dyes. [(C) 1999 Lippincott Williams & Wilkins.]