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dc.contributor.author
Alza, Natalia Paola
dc.contributor.author
Murray, Ana Paula
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Salvador, Gabriela Alejandra
dc.date.available
2018-04-05T23:52:46Z
dc.date.issued
2017-12
dc.identifier.citation
Alza, Natalia Paola; Murray, Ana Paula; Salvador, Gabriela Alejandra; Cativic acid-caffeic acid hybrid exerts cytotoxic effects and induces apoptotic death in human neuroblastoma cells; Springer; Naunyn-schmiedebergs Archives Of Pharmacology; 390; 12; 12-2017; 1229-1238
dc.identifier.issn
0028-1298
dc.identifier.uri
http://hdl.handle.net/11336/41039
dc.description.abstract
Background: The development of hybrids from natural products is a promising strategy for drug discovery. In cancer therapy, there is a need to discover novel agents that can induce apoptosis in cancer cells. To contribute to this field of interest, we investigated the effect of a synthetic hybrid from cativic acid and caffeic acid (5) on viability, proliferation and apoptosis in human neuroblastoma cells (IMR-32). Methods: Three hybrids were prepared via Mitsunobu esterification from 17-hydroxycativic acid (1) and natural phenols. Cell viability was analyzed by MTT assay. SYTOX green and LDH leakage were used to determine the cytotoxic effect. Caspase-3 activity, cell cycle phases and proliferation were analyzed in order to characterize the biological effects of hybrid 5. The mitogen-activated-protein kinase (MAPK) status was evaluated for elucidating the potential mechanisms involved in hybrid 5 effect. Results: Hybrid 5 reduced the viability of IMR-32 cells in a time- and concentration-dependent manner (IC50 = 18.0 ± 1.3 μM) as a result of its antiproliferative effect through changes in the cell cycle distribution and induction of apoptosis associated with activation of caspase-3. Exposure to 5 triggered ERK1/2 activation and nuclear translocation. Hybrid 5 also promoted an increase in nuclear localization of the transcription factor c-Jun. Inhibition of ERK1/2 and JNK potentiated 5-induced inhibition of IMR-32 viability.Conclusion: Hybrid 5 displays cell growth inhibition by promoting cell cycle arrest and apoptosis, through ERK1/2 and JNK participation.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Springer
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Hybrids
dc.subject
Cativic Acid
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Human Neuroblastoma
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Mapk
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Apoptosis
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Otras Ciencias Químicas
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Ciencias Químicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
Cativic acid-caffeic acid hybrid exerts cytotoxic effects and induces apoptotic death in human neuroblastoma cells
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-04-04T14:20:27Z
dc.identifier.eissn
1432-1912
dc.journal.volume
390
dc.journal.number
12
dc.journal.pagination
1229-1238
dc.journal.pais
Alemania
dc.description.fil
Fil: Alza, Natalia Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; Argentina
dc.description.fil
Fil: Murray, Ana Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; Argentina
dc.description.fil
Fil: Salvador, Gabriela Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
dc.journal.title
Naunyn-schmiedebergs Archives Of Pharmacology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://link.springer.com/10.1007/s00210-017-1421-0
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1007/s00210-017-1421-0
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