ArticleJournal of experimental & clinical cancer research : CR2013
Renal cancer-selective Englerin A induces multiple mechanisms of cell death and autophagy.
Article in Journal of experimental & clinical cancer research : CR, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 37 citations in OpenAlex.
- Review
- Therapeutic Potential of Natural Products in the Treatment of Renal Cell Carcinoma: A Review.Nutrients · 2022Review
- Natural products targeting cancer cell dependency.The Journal of antibiotics · 2021Review
- Long non-coding RNA HOTTIP affects renal cell carcinoma progression by regulating autophagy via the PI3K/Akt/Atg13 signaling pathway.Journal of cancer research and clinical oncology · 2019Article
- Cell death-related molecules and biomarkers for renal cell carcinoma targeted therapy.Cancer cell international · 2019Review
- Oxidopyrylium [5+2] Cycloaddition Chemistry: Historical Perspective and Recent Advances (2008-2018).Tetrahedron · 2018Article
- The Role of Compounds Derived from Natural Supplement as Anticancer Agents in Renal Cell Carcinoma: A Review.International journal of molecular sciences · 2017Review
- NaScientific reports · 2017Article
- Englerins: A Comprehensive Review.Journal of natural products · 2017Review
- Article
- Synthesis of a stable and orally bioavailable englerin analogue.Bioorganic & medicinal chemistry letters · 2016Article
- Synthesis and Biological Evaluation of New (-)-Englerin Analogues.ChemMedChem · 2016Article
- A potent betulinic acid analogue ascertains an antagonistic mechanism between autophagy and proteasomal degradation pathway in HT-29 cells.BMC cancer · 2016Article
- (-)-Englerin A is a potent and selective activator of TRPC4 and TRPC5 calcium channels.Angewandte Chemie (International ed. in English) · 2015Article
- Elaborating the role of natural products-induced autophagy in cancer treatment: achievements and artifacts in the state of the art.BioMed research international · 2015Review
- Englerin A Agonizes the TRPC4/C5 Cation Channels to Inhibit Tumor Cell Line Proliferation.PloS one · 2015Article
- Erratum: renal cancer-selective Englerin A induces multiple mechanisms of cell death and autophagy.Journal of experimental & clinical cancer research : CR · 2014Article
- Caffeine promotes autophagy in skeletal muscle cells by increasing the calcium-dependent activation of AMP-activated protein kinase.Biochemical and biophysical research communications · 2014Article
- The activation of c-Jun NH₂-terminal kinase is required for dihydroartemisinin-induced autophagy in pancreatic cancer cells.Journal of experimental & clinical cancer research : CR · 2014Article
- Metabolism modifications and apoptosis induction after Cellfood™ administration to leukemia cell lines.Journal of experimental & clinical cancer research : CR · 2013Article
Corrections and comments
- Erratum issued
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Renal cell carcinoma (RCC), the most common malignancy of the kidney, is refractory to standard therapy and has an incidence that continues to rise. Screening of plant extracts in search of new agents to treat RCC resulted in the discovery of englerin A (EA), a natural product exhibiting potent selective cytotoxicity against renal cancer cells. Despite the establishment of synthetic routes to the synthesis of EA, very little is known about its mechanism of action. The results of the current study demonstrate for the first time that EA induces apoptosis in A498 renal cancer cells in addition to necrosis. The induction of apoptosis by EA required at least 24 h and was caspase independent. In addition, EA induced increased levels of autophagic vesicles in A498 cells which could be inhibited by nonessential amino acids (NEAA), known inhibitors of autophagy. Interestingly, inhibition of autophagy by NEAA did not diminish cell death suggesting that autophagy is not a cell death mechanism and likely represents a cell survival mechanism which ultimately fails. Apart from cell death, our results demonstrated that cells treated with EA accumulated in the G2 phase of the cell cycle indicating a block in G2/M transition. Moreover, our results determined that EA inhibited the activation of both AKT and ERK, kinases which are activated in cancer and implicated in unrestricted cell proliferation and induction of autophagy. The phosphorylation status of the cellular energy sensor, AMPK, appeared unaffected by EA. The high renal cancer selectivity of EA combined with its ability to induce multiple mechanisms of cell death while inhibiting pathways driving cell proliferation, suggest that EA is a highly unique agent with great potential as a therapeutic lead for the treatment of RCC.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.