Induction of ER and mitochondrial stress by the alkylphosphocholine erufosine in oral squamous cell carcinoma cells

Cell Death & Disease
Shariq S AnsariMartin R Berger

Abstract

Endoplasmic reticulum (ER) plays an essential role in cell function and survival. Accumulation of unfolded or misfolded proteins in the lumen of the ER activates the unfolded protein response (UPR), resulting in ER stress and subsequent apoptosis. The alkylphosphocholine erufosine is a known Akt-mTOR inhibitor in oral squamous cell carcinoma (OSCC). In the present study, we evaluate erufosine's role to induce ER and mitochondrial stress leading to autophagy, apoptosis, and ROS induction. The cellular toxicity of erufosine was determined in two OSCC cell lines and gene expression and enrichment analyses were performed. A positive enrichment of ER stress upon erufosine exposure was observed, which was verified at protein levels for the ER stress sensors and their downstream mediators. Knockdown and pharmacological inhibition of the ER stress sensors PERK and XBP1 revealed their involvement into erufosine's cellular effects, including proliferation, apoptosis, and autophagy induction. Autophagy was confirmed by increased acidic vacuoles and LC3-B levels. Upon erufosine exposure, calcium influx into the cytoplasm of the two OSCC cell lines was seen. Apoptosis was confirmed by nuclear staining, Annexin-V, and immunoblotting of caspa...Continue Reading

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Citations

Jun 4, 2019·International Journal of Molecular Sciences·Olivier Pluquet, Antoine Galmiche
Oct 16, 2018·Anti-cancer Agents in Medicinal Chemistry·Ferda KaleağasıoğluMartin R Berger
Feb 2, 2019·Journal of Experimental & Clinical Cancer Research : CR·Zongyi WangZhengdong Cai
Nov 20, 2019·Medicinal Research Reviews·Tuhina KhanGiuseppe Campiani
Oct 9, 2019·International Journal of Molecular Sciences·Marineta KovachevaMartin R Berger
May 16, 2020·Frontiers in Pharmacology·Ferda KaleağasıoğluMartin R Berger
Apr 16, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Shanshan ChenXiaoli Zhu

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Datasets Mentioned

BETA
GSE96599

Methods Mentioned

BETA
Chip
PCR
electrophoresis
transfection
flow cytometry
gene knockdown

Software Mentioned

BD Accuri C6
limma
lumi
GraphPad Prism
GSEA
R
Bioconductor
Image J
imageJ

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