ArticleCell death & disease2018
Induction of ER and mitochondrial stress by the alkylphosphocholine erufosine in oral squamous cell carcinoma cells.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 43 citations in OpenAlex.
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- EP300 genomic redistribution following E-cadherin inhibition in MCF7 cancer cells: evidence for early epigenetic reprogramming.Histochemistry and cell biology · 2025Article
- TROP2 regulates cisplatin sensitivity of triple-negative breast cancer cells by regulating endoplasmic reticulum stress.Histology and histopathology · 2025Article
- Protective Effects of an Octapeptide Identified from Riceberry™ (Foods (Basel, Switzerland) · 2024Article
- ERp44 Regulates the Proliferation, Migration, Invasion, and Apoptosis of Gastric Cancer Cells Via Activation of ER Stress.Biochemical genetics · 2023Article
- Review
- The Impact of Oxidative Stress and AKT Pathway on Cancer Cell Functions and Its Application to Natural Products.Antioxidants (Basel, Switzerland) · 2022Review
- Stellettin B-Induced Oral Cancer Cell Death via Endoplasmic Reticulum Stress-Mitochondrial Apoptotic and Autophagic Signaling Pathway.International journal of molecular sciences · 2022Article
- Antineoplastic effects of erufosine on small cell and non-small cell lung cancer cells through induction of apoptosis and cell cycle arrest.Molecular biology reports · 2022Article
- Pharmacological drug screening to inhibit uveal melanoma metastatic cells eitherInternational journal of ophthalmology · 2022Article
- Dual Akt and Bcl-2 inhibition induces cell-type specific modulation of apoptotic and autophagic signaling in castration resistant prostate cancer cell lines.Molecular biology reports · 2021Article
- Mitochondrial Targeting Involving Cholesterol-Rich Lipid Rafts in the Mechanism of Action of the Antitumor Ether Lipid and Alkylphospholipid Analog Edelfosine.Pharmaceutics · 2021Review
- Lycorine hydrochloride induces reactive oxygen species-mediated apoptosis via the mitochondrial apoptotic pathway and the JNK signaling pathway in the oral squamous cell carcinoma HSC-3 cell line.Oncology letters · 2021Article
- Analysis of the correlation of the expression level of hypoxia-inducible factor-1α with the glycosylation of oral squamous cell carcinoma.American journal of translational research · 2021Article
- TSPYL5 activates endoplasmic reticulum stress to inhibit cell proliferation, migration and invasion in colorectal cancer.Oncology reports · 2020Article
- Nobiletin inhibits cell growth through restraining aerobic glycolysis via PKA-CREB pathway in oral squamous cell carcinoma.Food science & nutrition · 2020Article
- Multiple Facets of Autophagy and the Emerging Role of Alkylphosphocholines as Autophagy Modulators.Frontiers in pharmacology · 2020Review
- Conditional Knockdown of Osteopontin Inhibits Breast Cancer Skeletal Metastasis.International journal of molecular sciences · 2019Article
- Exosomes from Microglia Attenuate Photoreceptor Injury and Neovascularization in an Animal Model of Retinopathy of Prematurity.Molecular therapy. Nucleic acids · 2019Article
- Impact and Relevance of the Unfolded Protein Response in HNSCC.International journal of molecular sciences · 2019Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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 caspases. The induction of mitochondrial stress upon erufosine exposure was predicted by gene set enrichment analysis (GSEA) and shown by erufosine's effect on mitochondrial membrane potential, ATP, and ROS production in OSCC cells. These data show that ER and mitochondrial targeting by erufosine represents a new facet of its mechanism of action as well as a promising new framework in the treatment of head and neck cancers.
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