Paclitaxel induces apoptosis in Saos-2 cells with CD95L upregulation and Bcl-2 phosphorylation

Exp Cell Res. 1999 Oct 10;252(1):134-43. doi: 10.1006/excr.1999.4591.


We examined the effect of paclitaxel on human osteoblastic cells Saos-2 to determine if paclitaxel can affect proliferation and apoptosis. We used a p53-negative cell line in order to mimic the loss of function frequently observed at the clinical level. Paclitaxel induced cell death in a dose- and time-dependent manner. Marked nuclear condensation and fragmentation of chromatin were observed by Hoechst 33258 stain, DNA ladder formation, electron microscopy, and flow cytometry at concentrations as low as 100 nM, a concentration which can be achieved by infusion in human plasma. At 100 nM, paclitaxel induced a G2 arrest at 8 h of treatment. The cells then continued to accumulate in G2 until 72 h when the percentage of apoptotic events reached 54%. At the molecular level, Bcl-2 protein was phosphorylated at 16 h and PARP protein was cleaved, indicating the activation of caspase-3-like proteases. Caspase inhibitors Z-VAD-FMK and Z-DEVD-FMK rescued Saos-2 cells from paclitaxel-induced apoptosis. CD95 expression was constantly high, while CD95L showed a threefold increase in expression. This suggests that, following the G2 arrest, apoptosis is induced through the CD95/CD95L system.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Apoptosis / immunology
  • Apoptosis / physiology*
  • Caspases / physiology
  • Cell Cycle / drug effects
  • Cell Division / drug effects
  • Fas Ligand Protein
  • Humans
  • Membrane Glycoproteins / biosynthesis*
  • Microscopy, Electron
  • Osteoblasts / cytology
  • Osteoblasts / drug effects
  • Osteoblasts / physiology
  • Osteosarcoma / drug therapy
  • Osteosarcoma / pathology
  • Osteosarcoma / physiopathology
  • Paclitaxel / pharmacology*
  • Phosphorylation
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Tumor Cells, Cultured
  • Up-Regulation / drug effects
  • fas Receptor / metabolism


  • Antineoplastic Agents, Phytogenic
  • FASLG protein, human
  • Fas Ligand Protein
  • Membrane Glycoproteins
  • Proto-Oncogene Proteins c-bcl-2
  • fas Receptor
  • Caspases
  • Paclitaxel