Figure 2.

A, DMDA-PatA is not susceptible to PgP-mediated drug efflux. Compounds were tested side-by-side for growth-inhibitory effects in the drug-sensitive MES-SA cell line and its drug-resistant subline MES-SA/D×5-R×1. Growth-inhibitory IC₅₀ values were obtained. Drug resistance ratios were calculated as described in Materials and Methods. Paclitaxel, a known PgP substrate, was included as a positive control. B, DMDA-PatA is not cytotoxic to quiescent fibroblasts at doses that lead to antiproliferative effects. Cytotoxic effects of 24 h treatment with DMDA-PatA (closed circles) or carbonyl cyanide (closed squares; positive control) against quiescent IMR-90 human fibroblasts were determined as described in Materials and Methods. C, DMDA-PatA has potent antiproliferative activity against proliferating fibroblasts. IMR-90 human lung fibroblast cells were incubated in the presence of different concentrations of DMDA-PatA or DMSO control for 4 d. Methods of evaluation of cell growth are presented in Materials and Methods. IC₅₀ value was calculated as the concentration of a test compound resulting in cell growth equal to 50% of DMSO control treated cell preparations.