<i>N</i>-(4-hydroxyphenyl) retinamide (4HPR) enhances TRAIL-mediated apoptosis through enhancement of a mitochondrial-dependent amplification loop in ovarian cancer cell lines

Simple item page
dc.contributor.authorCuello, M
dc.contributor.authorCoats, AO
dc.contributor.authorDarko, I
dc.contributor.authorEttenberg, SA
dc.contributor.authorGardner, GJ
dc.contributor.authorNau, MM
dc.contributor.authorLiu, JR
dc.contributor.authorBirrer, MJ
dc.contributor.authorLipkowitz, S
dc.date.accessioned2025-01-21T01:08:04Z
dc.date.available2025-01-21T01:08:04Z
dc.date.issued2004
dc.description.abstractThe majority of ovarian cancer cells are resistant to apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Subtoxic concentrations of the semisynthetic retinoid N-(4-hydroxyphenyl)retinamide (4HPR) enhanced TRAIL-mediated apoptosis in ovarian cancer cell lines but not in immortalized nontumorigenic ovarian epithelial cells. The enhancement of TRAIL-mediated apoptosis by 4HPR was not due to changes in the levels of proteins known to modulate TRAIL sensitivity. The combination of 4HPR and TRAIL enhanced cleavage of multiple caspases in the death receptor pathway (including the two initiator caspases, caspase-8 and caspase-9). The 4HPR and TRAIL combination leads to mitochondrial permeability transition, significant increase in cytochrome c release, and increased caspase-9 activation. Caspase-9 may further activate caspase-8, generating an amplification loop. Stable overexpression of Bcl-xL abrogates the interaction between 4HPR and TRAIL at the mitochondrial level by blocking cytochrome c release. As a consequence, a decrease in activation of caspase-9, caspase-8, and TRAIL-mediated apoptosis occurs. These results indicate that the enhancement in TRAIL-mediated apoptosis induced by 4HPR is due to the increase in activation of multiple caspases involving an amplification loop via the mitochondrial-death pathway. These findings offer a promising and novel strategy for the treatment of ovarian cancer.
dc.fuente.origenWOS
dc.identifier.doi10.1038/sj.cdd.4401387
dc.identifier.eissn1476-5403
dc.identifier.issn1350-9047
dc.identifier.urihttps://doi.org/10.1038/sj.cdd.4401387
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/96419
dc.identifier.wosidWOS:000220879100005
dc.issue.numero5
dc.language.isoen
dc.pagina.final541
dc.pagina.inicio527
dc.revistaCell death and differentiation
dc.rightsacceso restringido
dc.subjectapoptosis
dc.subjectdeath receptors
dc.subjectfenretinide (4HPR)
dc.subjectovarian cancer
dc.subjectTRAIL
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.title<i>N</i>-(4-hydroxyphenyl) retinamide (4HPR) enhances TRAIL-mediated apoptosis through enhancement of a mitochondrial-dependent amplification loop in ovarian cancer cell lines
dc.typeartículo
dc.volumen11
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
Files
Collections
Artículos de revistas