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

Immunopharmacol Immunotoxicol. 1999 Nov;21(4):667-82. doi: 10.3109/08923979909007133.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / antagonists & inhibitors*
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • DNA Fragmentation / drug effects
  • Deferoxamine / pharmacology
  • G1 Phase / drug effects
  • Glutathione / analogs & derivatives
  • Glutathione / pharmacology
  • Growth Inhibitors / pharmacology
  • HL-60 Cells / cytology
  • HL-60 Cells / drug effects*
  • Humans
  • Mimosine / pharmacology
  • Nitric Oxide / physiology*
  • Nitroso Compounds / pharmacology
  • Paclitaxel / antagonists & inhibitors*
  • Paclitaxel / pharmacology*
  • S Phase / drug effects
  • S-Nitrosoglutathione

Substances

  • Antineoplastic Agents, Phytogenic
  • Growth Inhibitors
  • Nitroso Compounds
  • Nitric Oxide
  • Mimosine
  • S-Nitrosoglutathione
  • Glutathione
  • Deferoxamine
  • Paclitaxel