erucylphospho-n-n-n-trimethylpropylammonium has been researched along with Mouth-Neoplasms* in 3 studies
3 other study(ies) available for erucylphospho-n-n-n-trimethylpropylammonium and Mouth-Neoplasms
Article | Year |
---|---|
Induction of ER and mitochondrial stress by the alkylphosphocholine erufosine in oral squamous cell carcinoma cells.
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. Topics: Annexin A5; Antineoplastic Agents; Apoptosis; Autophagy; Calcium; Carcinoma, Squamous Cell; Cell Line, Tumor; Endoplasmic Reticulum; Endoplasmic Reticulum Stress; Humans; Membrane Potential, Mitochondrial; Microtubule-Associated Proteins; Mitochondria; Mouth Neoplasms; Organophosphates; Phosphorylcholine; Quaternary Ammonium Compounds | 2018 |
Erufosine increases RhoB expression in oral squamous carcinoma cells independent of its tumor suppressive mode of action - a short report.
Recently, we found that erufosine (erucylphospho-N,N,N trimethylpropylammonium) can induce up-regulation of RhoB expression in oral squamous carcinoma (OSCC) cells, thereby hinting at a tumor suppressive role. Therefore, we aimed to evaluate the role of RhoB in the tumor suppressive mode of action of erufosine on OSCC cells.. Anti-proliferative effects of erufosine were determined in HN-5 and FaDu OSCC-derived cells using a MTT assay. RhoB up-regulation was detected using microarray and qRT-PCR-based expression assays at IC. We found that after erufosine treatment of HN-5 and FaDu cells for 24, 48 and 72 h the IC. Our data show that erufosine can cause up-regulation of RhoB expression in OSCC cells. Combining erufosine treatment with siRNA-mediated RhoB knockdown did, however, not reveal a role of RhoB in its tumor suppressive mode of action. Topics: Antineoplastic Agents; Blotting, Western; Carcinoma, Squamous Cell; Cell Line, Tumor; Gene Knockdown Techniques; Humans; Mouth Neoplasms; Oligonucleotide Array Sequence Analysis; Organophosphates; Quaternary Ammonium Compounds; Real-Time Polymerase Chain Reaction; rhoB GTP-Binding Protein; Up-Regulation | 2017 |
Erufosine simultaneously induces apoptosis and autophagy by modulating the Akt-mTOR signaling pathway in oral squamous cell carcinoma.
We investigated the anticancer activity of erufosine in oral squamous carcinoma cell lines in terms of cell proliferation, colony formation, induction of autophagy/apoptosis, cell cycle and mTOR signaling pathway. Erufosine showed dose-dependent cytotoxicity in all cell lines, it induced autophagy as well as apoptosis, G2 cell cycle arrest and modulation of cyclin D1 expression. Further erufosine downregulated the phosphorylation of major components of mTOR pathway, like p-Akt at Ser473 and Thr308 residues, p-Raptor, p-mTOR, p-PRAS40 and its downstream substrates p-p70S6K and p-4EBP1 in a dose-dependent manner. The pre-treatment of tumor cells with p-mTOR siRNA increased cytotoxic effects of erufosine comparable to cisplatin but higher than rapamycin. Topics: Antineoplastic Agents; Apoptosis; Autophagy; Carcinoma, Squamous Cell; Cell Line, Tumor; Drug Screening Assays, Antitumor; Humans; Mouth Neoplasms; Organophosphates; Proto-Oncogene Proteins c-akt; Quaternary Ammonium Compounds; Signal Transduction; TOR Serine-Threonine Kinases | 2012 |