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 G2/M phases of cell cycle, induces apoptosis of leukemic cells, and activates macrophages to produce nitric oxide (NO) in response to interferon-gamma. NO has been found to play roles as pro-apoptotic or anti-apoptotic effector molecules. In this study, we investigate effects of NO on taxol-induced apoptosis in human myeloid leukemia cell, HL-60. Incubation of the cells with taxol for 24 hr induced marked DNA fragmentation of HL-60 cells. Treatment of the 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 100 nM taxol for 12 hr rendered the cells to be accumulated in G2/M phase, but the cotreatment of the cells with taxol and 0.1 mM GSNO decreased the accumulation of the cell in G2/M phases, suggesting that NO might interfere entering of taxol-treated cells into G2/M phases. Deferoxamine or mimosine, which can arrest cells mainly at G1/S phases, also decreased taxol-induced apoptosis and reduced the number of the taxol-treated cells arresting in G2/M phases. Thus, we conclude that a protective effect of NO on taxol-treated cells from apoptosis may be partially caused by interfering entering of the taxol-treated cells into G2/M phases.
Pae
H O
HO
Department of Microbiology and Immunology, Wonkwang University School of Medicine, Iksan, Chonbug, Korea.
Yoo
J C
JC
Choi
B M
BM
Kang
C L
CL
Kim
J D
JD
Chung
H T
HT
D000972:Antineoplastic Agents, Phytogenic / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053938:DNA Fragmentation / Q000187:drug effects; D003676:Deferoxamine / Q000494:pharmacology; D016193:G1 Phase / Q000187:drug effects; D005978:Glutathione / Q000031:analogs & derivatives / Q000494:pharmacology; D006131:Growth Inhibitors / Q000494:pharmacology; D018922:HL-60 Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D008898:Mimosine / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D009603:Nitroso Compounds / Q000494:pharmacology; D017239:Paclitaxel / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D016196:S Phase / Q000187:drug effects; D026422:S-Nitrosoglutathione
D000972:Antineoplastic Agents, Phytogenic; D006131:Growth Inhibitors; D009603:Nitroso Compounds; D009569:Nitric Oxide; D008898:Mimosine; D026422:S-Nitrosoglutathione; D005978:Glutathione; D003676:Deferoxamine; D017239:Paclitaxel