ArticleCell death & disease2011
Involvement of lipid rafts in the localization and dysfunction effect of the antitumor ether phospholipid edelfosine in mitochondria.
Article in Cell death & disease, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 65 citations in OpenAlex.
- Cholesterol-driven mitochondrial rejuvenation by quercetin nanotherapeutics restores implant osseointegration in diabetes.Bioactive materials · 2026Article
- Clusters of apoptotic signaling molecule-enriched rafts, CASMERs: membrane platforms for protein assembly in Fas/CD95 signaling and targets in cancer therapy.Biochemical Society transactions · 2022Article
- Defueling the cancer: ATP synthase as an emerging target in cancer therapy.Molecular therapy oncolytics · 2021Review
- Article
- Review
- Mitochondrial Targeting Involving Cholesterol-Rich Lipid Rafts in the Mechanism of Action of the Antitumor Ether Lipid and Alkylphospholipid Analog Edelfosine.Pharmaceutics · 2021Review
- Warburg's Ghost-Cancer's Self-Sustaining Phenotype: The Aberrant Carbon Flux in Cholesterol-Enriched Tumor Mitochondria via Deregulated Cholesterogenesis.Frontiers in cell and developmental biology · 2021Review
- Reply to Letter to the Editor.Neuro-oncology · 2020Article
- Lipid rafts as signaling hubs in cancer cell survival/death and invasion: implications in tumor progression and therapy: Thematic Review Series: Biology of Lipid Rafts.Journal of lipid research · 2020Review
- Evaluation of cell damage induced by irradiated Zinc-Phthalocyanine-gold dendrimeric nanoparticles in a breast cancer cell line.Biomedical journal · 2018Article
- The potent effect of mycolactone on lipid membranes.PLoS pathogens · 2018Article
- Mitochondria and lipid raft-located FOF1-ATP synthase as major therapeutic targets in the antileishmanial and anticancer activities of ether lipid edelfosine.PLoS neglected tropical diseases · 2017Article
- The alkyllysophospholipid edelfosine enhances TRAIL-mediated apoptosis in gastric cancer cells through death receptor 5 and the mitochondrial pathway.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Modulation of Mitochondrial Antiviral Signaling by Human Herpesvirus 8 Interferon Regulatory Factor 1.Journal of virology · 2016Article
- Endoplasmic reticulum targeting in Ewing's sarcoma by the alkylphospholipid analog edelfosine.Oncotarget · 2015Article
- Mitochondrial Ca(2+) Remodeling is a Prime Factor in Oncogenic Behavior.Frontiers in oncology · 2015Review
- Raft-like membrane domains in pathogenic microorganisms.Current topics in membranes · 2015Review
- Inositoylated platelet-activating factor (Ino-C2-PAF) modulates dynamic lymphocyte-endothelial cell interactions and alleviates psoriasis-like skin inflammation in two complementary mouse models.The Journal of investigative dermatology · 2014Article
- Lipid analogues as potential drugs for the regulation of mitochondrial cell death.British journal of pharmacology · 2014Review
- Lipids and cell death in yeast.FEMS yeast research · 2014Review
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lipid rafts and mitochondria are promising targets in cancer therapy. The synthetic antitumor alkyl-lysophospholipid analog edelfosine (1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine) has been reported to target lipid rafts. Here, we have found that edelfosine induced loss of mitochondrial membrane potential and apoptosis in human cervical carcinoma HeLa cells, both responses being abrogated by Bcl-x(L) overexpression. We synthesized a number of new fluorescent edelfosine analogs, which preserved the proapoptotic activity of the parent drug, and colocalized with mitochondria in HeLa cells. Edelfosine induced swelling in isolated mitochondria, indicating an increase in mitochondrial membrane permeability. This mitochondrial swelling was independent of reactive oxygen species generation. A structurally related inactive analog was unable to promote mitochondrial swelling, highlighting the importance of edelfosine molecular structure in its effect on mitochondria. Raft disruption inhibited mitochondrial localization of the drug in cells and edelfosine-induced swelling in isolated mitochondria. Edelfosine promoted a redistribution of lipid rafts from the plasma membrane to mitochondria, suggesting a raft-mediated link between plasma membrane and mitochondria. Our data suggest that direct interaction of edelfosine with mitochondria eventually leads to mitochondrial dysfunction and apoptosis. These observations unveil a new framework in cancer chemotherapy that involves a link between lipid rafts and mitochondria in the mechanism of action of an antitumor drug, thus opening new avenues for cancer treatment.
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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.