Paclitaxel-induced FasL-independent apoptosis and slow (non-apoptotic) cell death

Cancer Biol Ther. Mar-Apr 2002;1(2):113-7. doi: 10.4161/cbt.53.

Abstract

Microtubule-active drugs, including paclitaxel (Taxol, PTX), cause mitotic arrest, and this can result in apoptosis. A recently study has reported that PTX mediates apoptosis by upregulating FasL in Jurkat and MDA-231 cells. In contrast to the previous report, we found that anti-FasL antibodies failed to inhibit PTX-induced apoptosis in Jurkat cells. In MDA-231 cells, neither FasL nor PTX induced apoptosis. In these cells, PTX caused slow cell death without activation of caspase-3 or -8 or PARP cleavage. Doxorubicin at cytostatic concentrations did not affect FasL-induced apoptosis but inhibited PTX-induced apoptosis in Jurkat cells. Following PTX-induced mitotic arrest Jurkat cells undergo apoptosis, whereas MDA-MB-231 cells exit mitosis and form multinucleated cells which then die in a slower non-apoptotic manner.

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Cell Death / drug effects*
  • Doxorubicin / pharmacology
  • Fas Ligand Protein
  • Humans
  • Membrane Glycoproteins / physiology*
  • Paclitaxel / pharmacology*
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents, Phytogenic
  • FASLG protein, human
  • Fas Ligand Protein
  • Membrane Glycoproteins
  • Doxorubicin
  • Paclitaxel