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Plant ribosome-inactivating proteins type II induce the unfolded protein response in human cancer cells

C Horrix1, Z Raviv, E Flescher

  • 1Toxicology and Chemotherapy Unit, German Cancer Research Center, Im Neuenheimer Feld 581, 69120, Heidelberg, Germany. c.horrix@dkfz.de

Cellular and Molecular Life Sciences : CMLS
|September 17, 2010
PubMed

Insights

Type II ribosome-inactivating proteins (RIPs) trigger the unfolded protein response (UPR) in cancer cells, challenging the traditional view of translational arrest as the sole mechanism of toxicity. This UPR induction better explains cellular effects at specific RIP concentrations.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Toxicology

Background:

  • Type II ribosome-inactivating proteins (RIPs), like ricin, are studied for anti-cancer potential but also as bioweapons.
  • The precise molecular mechanism of RIP toxicity, particularly the role of 28S rRNA depurination and translational arrest, is debated.

Purpose of the Study:

  • To investigate the cellular response to type II RIPs (ricin, riproximin, volkensin) in cancer cell lines.
  • To elucidate the molecular mechanism of RIP-induced cell death, focusing on the unfolded protein response (UPR).

Main Methods:

  • Microarray analysis
  • Quantitative reverse transcription PCR (qRT-PCR)
  • Western blotting
  • Exposure of HCT116 and MDA-MB-231 cells to type II RIPs.

Main Results:

  • Type II RIPs induced the unfolded protein response (UPR) in HCT116 and MDA-MB-231 cells.
  • Apoptosis occurred at RIP concentrations where UPR-related gene translation persisted despite ribosomal depurination.
  • This suggests a more complex mechanism than general translational arrest.

Conclusions:

  • UPR induction is a key cellular response to type II RIP exposure.
  • The findings challenge the paradigm that irreversible 28S rRNA depurination solely causes general translational arrest and cell death.
  • UPR induction offers a more accurate model for understanding RIP cellular effects at specific concentrations.

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