RT info:eu-repo/semantics/article
T1 Irvalec inserts into the plasma membrane causing rapid loss of integrity and necrotic cell death in tumor cells
A1 Molina Guijarro, José Manuel
A1 Macías, Álvaro
A1 García Rodríguez, Carolina
A1 Muñoz Conejero, Eva
A1 García Fernández, Luis F.
A1 David, Miren
A1 Núñez Llorente, Lucía
A1 Martínez Leal, Juan Fernando
A1 Moneo, Victoria
A1 Cuevas, Carmen
A1 Lillo, María Pilar
A1 Villalobos Jorge, Carlos
A1 Valenzuela, Carmen
A1 Galmarini, Carlos María
K1 Antitumor drugs
K1 Fármacos antitumorales
K1 Plasma membrane
K1 Membrana plasmática
AB Irvalec 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 Ca2+ 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 Zn2+. 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.
PB Public Library of Science
SN 1932-6203
YR 2011
FD 2011
LK http://uvadoc.uva.es/handle/10324/45067
UL http://uvadoc.uva.es/handle/10324/45067
LA eng
NO PLoS ONE, 2011, vol. 6, n. 4. 13 p.
NO Producción Científica
DS UVaDOC
RD 24-nov-2024