Alternative pathways of programmed cell death are activated in cells with defective caspase-dependent apoptosis

Leuk Res. 2008 Apr;32(4):599-609. doi: 10.1016/j.leukres.2007.05.012. Epub 2007 Jul 6.

Abstract

Loss of programmed cell death pathways is one of the features of malignancy that complicate the response of cancer cells to a therapy. Activation of alternative cell death pathways offers a promising approach to enhance efficiency of cancer chemotherapy. We analysed programmed cell death pathways of v-myb-transformed BM2 monoblasts induced by arsenic trioxide, cycloheximide and camptothecin with U937 promonocytes as a reference cell line. We show that induced death of BM2 cells is not executed by caspases but rather by alternative cell death pathways. Camptothecin induces the lysosome-dependent cell death, arsenic trioxide induces autophagy, and most of cycloheximide-treated BM2 cells die by necrosis. The fact that alternative cell death pathways can be switched in cells with defects in activation and/or function of caspases suggests that understanding and targeting of these pathways could improve therapy of cancer cells suffering from defective apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Arsenic Trioxide
  • Arsenicals / pharmacology
  • Autophagy / drug effects*
  • Blotting, Western
  • Camptothecin / pharmacology
  • Caspases / metabolism*
  • Cell Line, Transformed
  • Cell Transformation, Neoplastic / pathology*
  • Chickens
  • Cycloheximide / pharmacology
  • Genes, myb / physiology
  • Humans
  • Microscopy, Fluorescence
  • Necrosis
  • Oxides / pharmacology
  • Signal Transduction / drug effects*
  • U937 Cells / drug effects

Substances

  • Antineoplastic Agents
  • Arsenicals
  • Oxides
  • Cycloheximide
  • Caspases
  • Arsenic Trioxide
  • Camptothecin