[Action mechanisms of zinostatin stimalamer (YM881)]

The mechanism of action of zinostatin stimalamer (YM881) was studied. YM881 suppressed colony formation of HeLa cells dose-dependently, and showed cytocidal activity. The compound inhibited DNA synthesis, but neither RNA nor protein synthesis in L1210 cells, and caused cellular DNA strand breaks in HeLa cells and DNA cleavage of PM2 phage supercoiled DNA. YM881 was also shown to cause typical G2/M arrest on L1210 cell cycle, and inhibited DNA polymerase alpha of HeLa cells, but only at high concentrations. Present study showed that antitumor and cytotoxic mechanisms of YM881 were identical to neocarzinostatin (NCS) and due to the cellular DNA strand breaks caused by direct DNA-cleaving activity and the subsequent inhibition of DNA synthesis.