RESUMO
The antitumor effect of flavone acetic acid, LM975, and its diethylaminoethyl ester derivative, LM985, was studied in four human malignant cell lines [WiDr, a colon carcinoma; LICR (LON) HN-3, a tongue carcinoma; MCF7, a breast carcinoma; K-562, a leukemia] using a colorimetric assay based on the reduction of dimethylthiazol-2-yl-diphenyltetrazolium. The cell lines were exposed continuously for 4-6 days to drug concentrations ranging between 0.1 and 500 micrograms/ml. For LM975, the concentrations inhibiting the growth of the various cell lines by 50% were 200 +/- 10, 97 +/- 7, 171 +/- 16 and greater than 500 micrograms/ml for LICR (LON) HN-3, WiDr, MCF-7, and K-562, respectively. The corresponding concentrations for LM985 were 151 +/- 3, 36 +/- 4, 86 +/- 3 and 140 +/- 18 micrograms/ml, respectively. The difference between LM985 and LM975 was statistically significant for the WiDr and LICR (LON) HN-3 lines. We also evaluated the cytotoxic activity of the two agents on normal human marrow myeloid progenitor cells in a colony-forming assay. Continuous exposure to the drugs gave a dose-dependent inhibition. The concentrations inhibiting the growth by 50% were 76 +/- 31 micrograms/ml for LM975 and 134 +/- 41 micrograms/ml for LM985. One hour incubation with either compound had no toxic effect on the myeloid progenitor cells. In conclusion, LM975 and LM985 do not appear to have a specific cytotoxicity for tumor cells. Our results indicate that, in vitro, toxicity on bone marrow myeloid progenitor cells is concentration dependent. Considering the low plasma concentration found in man after i.v. administration of LM985, our observations correlate well with the absence of drug-induced myelosuppression in patients.
