ArticlePloS one2017
Englerin A induces an acute inflammatory response and reveals lipid metabolism and ER stress as targetable vulnerabilities in renal cell carcinoma.
Article in PloS one, 2017. 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, 34 citations in OpenAlex.
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- Plasma Membrane Channel TRPM4 Mediates Immunogenic Therapy-Induced Necrosis.Cancer research · 2023Article
- Endoplasmic Reticulum Stress in Renal Cell Carcinoma.International journal of molecular sciences · 2023Review
- Ion channels and channelopathies in glomeruli.Physiological reviews · 2023Review
- A novel autophagy-related long non-coding RNAs prognostic risk score for clear cell renal cell carcinoma.BMC urology · 2022Article
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- The key role of sphingolipid metabolism in cancer: New therapeutic targets, diagnostic and prognostic values, and anti-tumor immunotherapy resistance.Frontiers in oncology · 2022Review
- Integration analysis identifies MYBL1 as a novel immunotherapy biomarker affecting the immune microenvironment in clear cell renal cell carcinoma: Evidence based on machine learning and experiments.Frontiers in immunology · 2022Article
- Silver nanoparticle-induced alteration of mitochondrial and ER homeostasis affects human breast cancer cell fate.Toxicology reports · 2022Article
- Regulation of the PTEN/PI3K/AKT pathway in RCC using the active compounds of natural productsMolecular medicine reports · 2021Article
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- Computational Approaches for Cancer-Fighting: From Gene Expression to Functional Foods.Cancers · 2021Article
- Tannic acid attenuates vascular calcification-induced proximal tubular cells damage through paracrine signaling.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2021Article
- Canonical transient receptor potential channels and their modulators: biology, pharmacology and therapeutic potentials.Archives of pharmacal research · 2021Review
- Vulnerability of subcellular structures to pathogenesis induced by rotenone in SH-SY5Y cells.Physiological research · 2021Article
- Emerging Landscapes of Tumor Immunity and Metabolism.Frontiers in oncology · 2020Review
- Treasure troves of pharmacological tools to study transient receptor potential canonical 1/4/5 channels.British journal of pharmacology · 2019Review
- NutriGenomeDB: a nutrigenomics exploratory and analytical platform.Database : the journal of biological databases and curation · 2019Article
- Abrogation of store-operated CaCell death discovery · 2019Article
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Renal cell carcinoma (RCC) is among the top ten most common forms of cancer and is the most common malignancy of the kidney. Clear cell renal carcinoma (cc-RCC), the most common type of RCC, is one of the most refractory cancers with an incidence that is on the rise. Screening of plant extracts in search of new anti-cancer agents resulted in the discovery of englerin A, a guaiane sesquiterpene with potent cytotoxicity against renal cancer cells and a small subset of other cancer cells. Though a few cellular targets have been identified for englerin A, it is still not clear what mechanisms account for the cytotoxicity of englerin A in RCC, which occurs at concentrations well below those used to engage the targets previously identified. Unlike any prior study, the current study used a systems biology approach to explore the mechanism(s) of action of englerin A. Metabolomics analyses indicated that englerin A profoundly altered lipid metabolism by 24 h in cc-RCC cell lines and generated significant levels of ceramides that were highly toxic to these cells. Microarray analyses determined that englerin A induced ER stress signaling and an acute inflammatory response, which was confirmed by quantitative PCR and Western Blot analyses. Additionally, fluorescence confocal microscopy revealed that englerin A at 25 nM disrupted the morphology of the ER confirming the deleterious effect of englerin A on the ER. Collectively, our findings suggest that cc-RCC is highly sensitive to disruptions in lipid metabolism and ER stress and that these vulnerabilities can be targeted for the treatment of cc-RCC and possibly other lipid storing cancers. Furthermore, our results suggest that ceramides may be a mediator of some of the actions of englerin A. Lastly, the acute inflammatory response induced by englerin A may mediate anti-tumor immunity.
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