RESUMEN
Estrogen receptor (ER) antagonists have been widely used for breast cancer treatment; however, patients have increasingly shown resistance and sensitivity to the high toxicity of these drugs, and identification of novel targeted therapies is therefore required. To determine whether nemorosone, a polycyclic polyisoprenylated benzophenone isolated from floral resins of Clusia rosea Jacq. and Cuban propolis samples, exerts anticancer effects on human breast cancer cells, estrogen receptor positive (ERα+) MCF-7 and estrogen receptor negative (ERα-) MDA-MB-231 and LNCaP cells were used. Cells were treated with nemorosone alone or in association with 17ß-estradiol (E2) or an ER antagonist, ICI 182,780, a selective ER downregulator that completely abrogates estrogen-sensitive gene transcription. Nemorosone inhibited the cell viability of ERα+ but not of ERα- cells. In MCF-7, nemorosone induced inhibition of cell growth by blocking the cell cycle in the G0/G1 phase. Moreover, the expression of pERK1/2 and pAkt, considered to be hallmarks of the nongenomic estrogen signalling pathway, were reduced in MCF-7 cells treated with nemorosone. All these effects were enhanced by ICI 182,780. However, nemorosone was not able to interfere with E2-induced Ca²(+) release. These findings suggest that nemorosone may have therapeutic application in the treatment of breast cancer because of its activity on ERα.
Asunto(s)
Antineoplásicos Fitogénicos/toxicidad , Benzofenonas/toxicidad , Neoplasias de la Mama/patología , Clusia , Citotoxinas/toxicidad , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/uso terapéutico , Benzofenonas/aislamiento & purificación , Benzofenonas/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Señalización del Calcio/efectos de los fármacos , Señalización del Calcio/fisiología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Citotoxinas/aislamiento & purificación , Citotoxinas/uso terapéutico , Femenino , Humanos , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/uso terapéutico , Extractos Vegetales/toxicidadRESUMEN
Gap junctions (GJs) channels provide the basis for intercellular communication in the cardiovascular system for maintenance of the normal cardiac rhythm, regulation of vascular tone and endothelial function as well as metabolic interchange between the cells. They allow the transfer of small molecules and may enable slow calcium wave spreading, transfer of "death" or of "survival" signals. In the cardiomyocytes the most abundant isoform is Connexin 43 (Cx43). Alterations in Cx43 expression and distribution were observed in myocardium disease; i.e. in hypertrophic cardiomyopathy, heart failure and ischemia. Recent reports suggest the presence of Cx43 in the mitochondria as well, at least in the inner mitochondrial membrane, where it plays a central role in ischemic preconditioning. In this review, the current knowledge on the relationship between the remodeling of cardiac gap junctions and cardiac diseases are summarized.