@misc{10481/59038,
year = {2019},
month = {2},
url = {http://hdl.handle.net/10481/59038},
abstract = {Despite 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.},
organization = {This 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”.},
publisher = {MDPI},
keywords = {Gef gene},
keywords = {Apoptin gene},
keywords = {Combined therapy},
keywords = {Apoptosis},
keywords = {Necrosis},
keywords = {Pore},
title = {Deciphering the Mechanism of Action Involved in Enhanced Suicide Gene Colon Cancer Cell Killer Effect Mediated by Gef and Apoptin},
doi = {10.3390/cancers11020264},
author = {Cáceres, Blanca and Ramírez, Alberto and Carrillo Delgado, Esmeralda Esperanza and Jiménez, Gema and Griñán Lisón, Carmen and López Ruiz, Elena and Jiménez Martínez, Yaiza and Marchal Corrales, Juan Antonio and Boulaiz Tassi, Houria},
}