Apoptotic cell death induced by taxol is inhibited by nitric oxide in human-leukemia HL-60 cells

Taxol, an antineoplastic drug, increases the fraction of cells in G(2)/M ph ases of cell cycle, induces apoptosis of leukemic cells, and activates macr ophages to produce nitric oxide:(NO) in response to interferon-gamma. NO ha s been found to play roles as pro-apoptotic or anti-apoptotic effector mole cules. In this study,we investigate effects of NO on taxol-induced apoptosi s in human: myeloid leukemia cell, HL-60. Incubation of the cells with taxo l for 24hr induced marked DNA fragmentation of HL-60 cells. Treatment of th e cells with S-nitrosogluthathione (GSNO), a NO-generating agent, protected the cells against taxol-induced apoptosis. Cell cycle analysis showed that treatment of the cells with 100nM taxol for 12hr rendered the cells to be accumulated in G(2)/M phase, but the cotreatment of the cells with taxol an d 0.1mM GSNO decreased the accumulation of the cell in G(2)/M phases, sugge sting that NO might interfere entering of taxol-treated cells into G(2)/M p hases. Deferoxamine or mimosine, which can arrest cells mainly at G(1)/S ph ases, also decreased taxol-induced apoptosis and reduced the number of the taxol-treated cells arresting in G(2)/M phases. Thus, we conclude that a pr otective effect of NO on taxol-treated cells from apoptosis may be partiall y caused by interfering entering of the taxol-treated cells into G(2)/M pha ses.