Inhibition of human topoisomerase I and activation of caspase-3 by aza-angucyclinones and arylaminopyrimido[4,5-c]isoquinoline-7,10-quinones

Simple item page
dc.contributor.authorMonsalve, Francisco A.
dc.contributor.authorValderrama, Jaime A.
dc.contributor.authorVasquez, David
dc.contributor.authorIbacache, Andrea
dc.contributor.authorRodriguez, Jaime A.
dc.contributor.authorGonzalez, Daniel R.
dc.contributor.authorLeiva, Elba
dc.contributor.authorGonzalez, Enrique
dc.date.accessioned2024-01-10T12:06:05Z
dc.date.available2024-01-10T12:06:05Z
dc.date.issued2012
dc.description.abstractCancer is the second cause of death in the world after cardiovascular diseases. Cancer cells acquire capacities not present in normal cells, such as self-sufficiency, resistance to antiproliferative stimuli, evasion of apoptosis, unlimited replication, invasiveness and metastasis. Consequently, it is of major interest to explore and develop molecules with anticancer activity directed to specific targets. In this study, we aimed to evaluate two series of polycyclic quinones: aza-angucyclinone and arylaminopyrimido[4,5-c]isoquinoline-7,10-quinones, in their capacity to inhibit human topoisomerase I (TOP1) and to trigger apoptosis through activation of caspase-3. We evaluated the capacity of the two series of polycyclic quinones to inhibit TOP1, using a DNA supercoiled relaxation assay and their capacity to induce apoptosis through the activation of caspase-3 in HL60 cells. Both series of quinones inhibited TOP1 activity over 50%. When we evaluated the pro-apoptotic capacity of both series of quinones, at therapeutically relevant concentrations, the arylaminoquinones ADPA-ICC (methyl 7-(4-methoxyphenyl)amino-1,3-dimethyl-5,8-dioxo-5,8-dihydroisoquinoline-4-carboxylate), P4 (9-phenylamino-3,4-dihydrophenanthridine-1,7,10(2H)-trione) and the aza-angucyclinone OH-6H (8-hydroxy-2,4-dimethyl-2H,4H-benzo[g]pyrimido[4,5-c]isoquinoline-1,3,7,12-tetraone) increased the caspase-3 activity by approximately 2-fold over the control. The series of the arylaminoquinones and aza-angucyclinones showed differential antiproliferative capacity. We further identified a group of them that showed antiproliferative capacity possibly through inhibition of TOP1 and by activation of caspase-3. This group of molecules may represent a potential pharmacological tool in treatment against cancer.
dc.description.funderFondo Nacional de Ciencia y Tecnologia
dc.fechaingreso.objetodigital2024-05-30
dc.format.extent6 páginas
dc.fuente.origenWOS
dc.identifier.doi10.3892/ijmm.2012.961
dc.identifier.eissn1791-244X
dc.identifier.issn1107-3756
dc.identifier.pubmedidMEDLINE:22485249
dc.identifier.urihttps://doi.org/10.3892/ijmm.2012.961
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/76113
dc.identifier.wosidWOS:000304579600022
dc.information.autorucQuímica;Ibacache A;S/I;165677
dc.information.autorucQuímica;Valderrama J;S/I;98772
dc.information.autorucQuímica;Vasquez D ;S/I;117510
dc.issue.numero1
dc.language.isoen
dc.nota.accesoContenido parcial
dc.pagina.final156
dc.pagina.inicio151
dc.publisherSPANDIDOS PUBL LTD
dc.revistaINTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
dc.rightsacceso restringido
dc.subjecttopoisomerase 1
dc.subjectquinones
dc.subjectchemotherapeutic
dc.subjectinhibitor
dc.subjectcaspase-3
dc.subjectTRIPTYCENE BISQUINONES
dc.subjectCANCER CELLS
dc.subjectAPOPTOSIS
dc.subjectCAMPTOTHECIN
dc.subjectQUINONES
dc.subjectVITRO
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleInhibition of human topoisomerase I and activation of caspase-3 by aza-angucyclinones and arylaminopyrimido[4,5-c]isoquinoline-7,10-quinones
dc.typeartículo
dc.volumen30
sipa.codpersvinculados165677
sipa.codpersvinculados98772
sipa.codpersvinculados117510
sipa.indexWOS
sipa.trazabilidadCarga SIPA;09-01-2024
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Inhibition of human topoisomerase I and activation of caspase-3 by aza-angucyclinones and arylaminopyrimido[4,5-c]isoquinoline-7,10-quinones.pdf
Size:
3.29 KB
Format:
Adobe Portable Document Format
Description:
Download
Collections
Artículos de revistas