Increased gap junctional intercellular communication is directly related to the anti-tumor effect of all-trans-retinoic acid plus tamoxifen in a human mammary cancer cell line

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dc.contributor.authorSáez, CG
dc.contributor.authorVelásquez, L
dc.contributor.authorMontoya, M
dc.contributor.authorEugenín, E
dc.contributor.authorAlvarez, MG
dc.date.accessioned2025-01-21T01:09:21Z
dc.date.available2025-01-21T01:09:21Z
dc.date.issued2003
dc.description.abstractAdditive effects against tumor cells might be achieved by combining anti-neoplastic agents directed against one or more altered mechanisms in cancer. We investigated the participation of gap junctional intercellular communication (GJIC),which is commonly dysfunctional in tumor cells as a possible mediating mechanism of the effect of all-trans-retinoic acid (RA) and tamoxifen (Tx) in MCF-7 human breast cancer cell lines. The combination of RA+Tx stimulated GJIC in approximately 53+/-3% of MCF-7 cells as early as after 6 In of treatment remaining communicated through 144 h of culture. The GJIC enhancement occurred along with immunolocalization of Cx26 and 43 at the membrane of contacting cells and correlated with higher protein levels. Cx40 immunoreactive plaques were detected at cell-to-cell contacts during 48 h of RA+Tx treatment that did not involve higher protein expression, to the contrary, a downregulation occurred after 72 In of treatment. Cell proliferation inhibition upon RA+Tx exposure was observed with optimal effects at 96-120 h of culture with an accumulation of cells primarily in G2/M and G0/G1 cell cycle boundaries. An enhancement of the pre-existing E-cadherin levels was observed after drug exposure along with a downregulation of Bcl-2 and C-myc protein levels and a reduction of telomerase activity, suggesting partial tumor phenotype reversion. Blockage of the RA+Tx-induced GJIC with 18-beta-glycyrrhetinic acid (beta-Gly) prevented in 34% the inhibition of MCF-7 proliferation and the E-cadherin increment in 30% at 96 h of culture. GJIC blockage did not alter the downregulation of Bcl-2, c-Myc, or telomerase activity induced by RA+Tx. Our results showed the participation of GJIC as a mediator mechanism of the combined action of RA and Tx in MCF-7 cells. The chemopreventive modulation of GJIC might represent an approachable alternative for the improvement of cancer therapy.
dc.fuente.origenWOS
dc.identifier.doi10.1002/jcb.10519
dc.identifier.eissn1097-4644
dc.identifier.issn0730-2312
dc.identifier.urihttps://doi.org/10.1002/jcb.10519
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/96574
dc.identifier.wosidWOS:000183135500003
dc.issue.numero3
dc.language.isoen
dc.pagina.final461
dc.pagina.inicio450
dc.revistaJournal of cellular biochemistry
dc.rightsacceso restringido
dc.subjectgap junctional intercellular communication
dc.subjectchemoprevention
dc.subjectanti-tumor
dc.subjecthuman breast cancer cells
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleIncreased gap junctional intercellular communication is directly related to the anti-tumor effect of all-trans-retinoic acid plus tamoxifen in a human mammary cancer cell line
dc.typeartículo
dc.volumen89
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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