Human T-cell leukemia-derived Jurkat cells are known to be defective in the G I checkpoint. DNA-damaging agent bleomycin arrests the cell cycle at G2 phase of Jurkat cells, and microtubule-acting colchicine arrests it at the M phase. Simaomicin alpha, an actinomycete metabolite. itself showed no effect on the cell cycle status of Jurkat cells at least tip to 6.0 nM. However, the compound (0.6-6.0nM) was found to abrogate the bleomycin-induced G2 arrest, yielding a drastic decrease in cells at the G2 phase and increase in cells at the subG1 and G1 phases. Oil the other hand. the compound did not show any effect on the colchicine-induced M phase arrest in Jurkat cells. Furthermore, the compound showed almost no effect on the cell cycle status of the bleomycin-treated or -untreated normal cell line HUVEC. These data Suggested that simaomicin alpha disrupts the cell cycle G2 checkpoint of cancer cells selectively. leading to sensitization of cancer cells to anti-cancer reagents. (C) 2004 Elsevier Inc. All rights reserved.