期刊
CELLULAR SIGNALLING
卷 26, 期 2, 页码 419-432出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2013.10.004
关键词
Yessotoxin; Autophagic cell death; ER-stress; BNIP3; mTOR; Lipid metabolism
类别
资金
- Ministerio de Ciencia y Tecnologia, Spain [SAF2009-12581, AGL2009-13581-CO2-01, TRA2009-0189, AGL2010-17875]
- Xunta de Galicia, Spain [GRC 2010/10, PGDIT 07MMA006261PR, PGIDIT (INCITE) 09MMA003261PR, PGDIT (INCITE) 09261080PR, 2009/XA044, 10PXIB261254PR]
- EU [211326, 265896, 265409 muAQUA, 262649 BEADS, 312184 PharmaSea]
- Atlantic Area Programme (Interreg IVB Trans-national) [2009-1/117 Pharmatlantic]
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. (C) 2013 Elsevier Inc. All rights reserved.
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