Characterization of the anticancer activity of DW2282, a new anticancer agent

DW2282 [(S)-(+)-4-phenyl-1-[N-(4-aminobenzoyl) indoline-5-sulfonyl]-4,5-dih ydro-2-imidazolone] hydrochloride] was derived from diarylsulfonylurea and was identified as a prominent new anticancer agent. We examined the charact eristics of DW2282 activity on the proliferation of human lung carcinoma ce lls, A549 and human leukemic cells, K562. DW2282 effectively inhibited canc er cell proliferation in vitro. Colony forming assay and viability tests de monstrated that DW2282 is a cytotoxic agent rather than a cytostatic agent. The isotope uptake test exhibited that DW2282 inhibited or inactivated pro tein synthesis. Also, under conditions which cause RNA or protein synthesis inhibition, by co-treatment with actinomycin D or cycloheximide, reduced t he anticancer effects of DW2282. This means that the cytotoxicity of DW2282 depends partially on RNA or protein synthesis and proteins affected by DW2 282 may inactivate ol alter the process of the synthesis of another protein . DW2282 activity was highly diminished in the presence of colcemid, a meta phase spindle blocker. This result suggests that DW2282 may be related to t he cell cycle. After exposure to DW2282, morphologically apoptotic cells ap peared in A549 cells and fragmented DNA was detected in K562 cells. It demo nstrated that apoptosis is one of the mechanisms by which DW2282 inhibits t he proliferation of A549 and K562 cells.