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dc.contributor.authorCáceres, Blanca
dc.contributor.authorRamírez, Alberto
dc.contributor.authorCarrillo Delgado, Esmeralda Esperanza 
dc.contributor.authorJiménez, Gema
dc.contributor.authorGriñán Lisón, Carmen 
dc.contributor.authorLópez Ruiz, Elena
dc.contributor.authorJiménez Martínez, Yaiza
dc.contributor.authorMarchal Corrales, Juan Antonio 
dc.contributor.authorBoulaiz Tassi, Houria
dc.identifier.citationCáceres, B., Ramirez, A., Carrillo, E., Jimenez, G., Griñán-Lisón, C., López-Ruiz, E., ... & Boulaiz, H. (2019). Deciphering the Mechanism of Action Involved in Enhanced Suicide Gene Colon Cancer Cell Killer Effect Mediated by Gef and Apoptin. Cancers, 11(2), 264.es_ES
dc.description.abstractDespite the great advances in cancer treatment, colorectal cancer has emerged as the second highest cause of death from cancer worldwide. For this type of tumor, the use of suicide gene therapy could represent a novel therapy. We recently demonstrated that co-expression of gef and apoptin dramatically inhibits proliferation of the DLD-1 colon cell line. In the present manuscript, we try to establish the mechanism underlying the enhanced induction of apoptosis by triggering both gef and apoptin expression in colon tumor cells. Scanning microscopy reveals that simultaneous expression of gef and apoptin induces the apparition of many “pores” in the cytoplasmic membrane not detected in control cell lines. The formation of pores induced by the gef gene and accentuated by apoptin results in cell death by necrosis. Moreover, we observed the presence of apoptotic cells. Performing protein expression analysis using western blot, we revealed an activation of mitochondrial apoptosis (increased expression of Pp53, cytochrome c, Bax, and caspase 9) and also the involvement of the extrinsic pathway through caspase 8activation. In conclusion, in this manuscript we demonstrate for the first time that the extrinsic pathway of apoptosis and pore formation is also involved in the cell death caused by the co-expression of the gef and apoptin genes. Our results suggest that co-expression of gef and apoptin genes induces an increase in post-apoptotic necrotic cell death and could be a valuable tool in the design of new antitumor strategies focused on the enhancement of the immune response against cancer cell death.es_ES
dc.description.sponsorshipThis research was supported by the Fundación Mutua Madrileña (project FMM-AP16683-2017), Consejería de Salud Junta de Andalucía (PI-0089-2017), the Ministerio de Economía y Competitividad (MINECO, FEDER funds, grant number MAT2015-62644.C2.2.R) and from the Chair “Doctors Galera-Requena in cancer stem cell research”.es_ES
dc.rightsAtribución 3.0 España*
dc.subjectGef genees_ES
dc.subjectApoptin genees_ES
dc.subjectCombined therapyes_ES
dc.subjectNecrosis es_ES
dc.titleDeciphering the Mechanism of Action Involved in Enhanced Suicide Gene Colon Cancer Cell Killer Effect Mediated by Gef and Apoptines_ES

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Atribución 3.0 España
Except where otherwise noted, this item's license is described as Atribución 3.0 España