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
dc.contributor.author | Sáez, CG | |
dc.contributor.author | Velásquez, L | |
dc.contributor.author | Montoya, M | |
dc.contributor.author | Eugenín, E | |
dc.contributor.author | Alvarez, MG | |
dc.date.accessioned | 2025-01-21T01:09:21Z | |
dc.date.available | 2025-01-21T01:09:21Z | |
dc.date.issued | 2003 | |
dc.description.abstract | Additive 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.origen | WOS | |
dc.identifier.doi | 10.1002/jcb.10519 | |
dc.identifier.eissn | 1097-4644 | |
dc.identifier.issn | 0730-2312 | |
dc.identifier.uri | https://doi.org/10.1002/jcb.10519 | |
dc.identifier.uri | https://repositorio.uc.cl/handle/11534/96574 | |
dc.identifier.wosid | WOS:000183135500003 | |
dc.issue.numero | 3 | |
dc.language.iso | en | |
dc.pagina.final | 461 | |
dc.pagina.inicio | 450 | |
dc.revista | Journal of cellular biochemistry | |
dc.rights | acceso restringido | |
dc.subject | gap junctional intercellular communication | |
dc.subject | chemoprevention | |
dc.subject | anti-tumor | |
dc.subject | human breast cancer cells | |
dc.subject.ods | 03 Good Health and Well-being | |
dc.subject.odspa | 03 Salud y bienestar | |
dc.title | 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 | |
dc.type | artículo | |
dc.volumen | 89 | |
sipa.index | WOS | |
sipa.trazabilidad | WOS;2025-01-12 |