Yessotoxin induces ER-stress followed by autophagic cell death in glioma cells mediated by mTOR and BNIP3.

Abstract

Yessotoxin at nanomolar concentrations can induce programmed cell death in different model systems. Paraptosis-like cell death induced by YTX in BC3H1 cells, which are insensitive to several caspase inhibitors,has also been reported. This makes yessotoxin of interest in the search of molecules that target cancer cells vulnerabilities when resistance to apoptosis is observed. To better understand the effect of this molecule at the molecular level on tumor cells, we conducted a transcriptomic analysis using 3 human glioma cell lines with different sensitivities to yessotoxin. We show that the toxin induces a deregulation of the lipid metabolism in glioma cells as a consequence of induction of endoplasmic reticulum stress. The endoplasmic reticulum stress in turn arrests the cell cycle and inhibits the protein synthesis. In the three cell lines used we show that YTX induces autophagy, which is involved in cell death. The sensibility of the cell lines used towards autophagic cell death was related to their doubling time, being the cell line with the lowest proliferation rate the most resistant.The involvement of mTOR and BNIP3 in the autophagy induction was also determined.

• Authors: J A Rubiolo, H López-Alonso, P Martínez, A Millán, E Cagide, M R Vieytes, F V Vega, L M Botana
• Journal: Cellular signalling (Cell Signal) Vol. 26 Issue 2 Pg. 419-32 (Feb 2014) ISSN: 1873-3913 [Electronic] England
• PMID: 24511615 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• BNIP3 protein, human
• DDIT3 protein, human
• DDIT4 protein, human
• Membrane Proteins
• Mollusk Venoms
• Oxocins
• Proto-Oncogene Proteins
• RNA, Small Interfering
• Transcription Factors
• Transcription Factor CHOP
• Cholesterol
• MTOR protein, human
• TOR Serine-Threonine Kinases
• yessotoxin

Topics

• Autophagy (drug effects)
• Cell Cycle Checkpoints (drug effects)
• Cell Line, Tumor
• Cholesterol (metabolism)
• Cluster Analysis
• Down-Regulation (drug effects)
• Endoplasmic Reticulum Stress (drug effects)
• Glioma (metabolism, pathology)
• Humans
• Membrane Proteins (antagonists & inhibitors, genetics, metabolism)
• Mollusk Venoms
• Oxocins (toxicity)
• Proto-Oncogene Proteins (antagonists & inhibitors, genetics, metabolism)
• RNA Interference
• RNA, Small Interfering (metabolism)
• Signal Transduction (drug effects)
• TOR Serine-Threonine Kinases (metabolism)
• Transcription Factor CHOP (antagonists & inhibitors, genetics, metabolism)
• Transcription Factors (antagonists & inhibitors, genetics, metabolism)
• Up-Regulation (drug effects)