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Irvalec inserts into the plasma membrane causing rapid loss of integrity and necrotic cell death in tumor cells

AuthorsMolina-Guijarro, José M.; Macías, Álvaro; García, Carolina ; Muñoz, Eva ; García-Fernández, Luis F. ; David, Miren ; Núñez, Lucía ; Lillo, M. Pilar ; Villalobos, Carlos ; Valenzuela, Carmen
Hkv1.5 channels
Issue Date27-Apr-2011
PublisherPublic Library of Science
CitationPLoS ONE 6(4): e19402 (2011)
AbstractIrvalec is a marine-derived antitumor agent currently undergoing phase II clinical trials. In vitro, Irvalec induces a rapid loss of membrane integrity in tumor cells, accompanied of a significant Ca(2+) influx, perturbations of membrane conductivity, severe swelling and the formation of giant membranous vesicles. All these effects are not observed in Irvalec-resistant cells, or are significantly delayed by pretreating the cells with Zn(2+). Using fluorescent derivatives of Irvalec it was demonstrated that the compound rapidly interacts with the plasma membrane of tumor cells promoting lipid bilayer restructuration. Also, FRET experiments demonstrated that Irvalec molecules localize in the cell membrane close enough to each other as to suggest that the compound could self-organize, forming supramolecular structures that likely trigger cell death by necrosis through the disruption of membrane integrity.
DescriptionThis is an open-access article distributed under the terms of the Creative Commons Attribution License.-- et al.
Publisher version (URL)http://dx.doi.org/10.1371/journal.pone.0019042
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