Effect of tamoxifen and retinoic acid on bradykinin induced proliferation in MCF-7 cells.
Chemopreventive approaches for the treatment of breast cancer have been validated clinically and with in vitro studies. The combined action of tamoxifen/all-trans retinoic acid was advantageous in MCF-7 cells, reducing cell proliferation, Bcl-2 and c-Myc protein levels and increasing E-Cadherin protein levels and Gap junctional Intercellular Communication. We further investigated their combined effect in the presence of bradykinin, a pro-inflammatory agent, previously reported to contribute to the proliferation of breast cancer cells. Bradykinin increased MCF-7 cell proliferation, c-Myc levels and ERK1/2 activity. The co-incubation of bradykinin-MCF-7 cells with tamoxifen/all-trans retinoic acid reduced cell proliferation, ERK1/2 activity, as well as Bcl-2, c-Myc, and bradykinin receptor-2 levels, without altering the enhanced E-cadherin levels induced by tamoxifen/all-trans retinoic acid. We showed that the anti-tumoral effect of tamoxifen/all-trans retinoic acid is beneficial in MCF-7 breast cancer cells grown in a bradykinin-pro-mitogenic environment, an effect that might be, at least in part, through the MAPK pathway and B2-bradykinin receptor inhibition.
Searovic
Paola
P
Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
Alonso
Marcelo
M
Oses
Carolina
C
Pereira-Flores
Karla
K
Velarde
Victoria
V
Saez
Claudia G
CG
D001920:Bradykinin / Q000494:pharmacology*; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D043782:Receptor, Bradykinin B2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013629:Tamoxifen / Q000494:pharmacology*; D014212:Tretinoin / Q000494:pharmacology*
D015820:Cadherins; C489427:MYC protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D043782:Receptor, Bradykinin B2; D013629:Tamoxifen; D014212:Tretinoin; D001920:Bradykinin