title: Inhibitory effect of cytotoxic stilbenes related to resveratrol on the expression of the VEGF, hTERT and c-Myc genes.
abstract: A group of thirty-nine stilbene derivatives, prepared by means of Heck coupling reactions, has been investigated for their cytotoxicity, as well as for their ability to inhibit the production of the vascular endothelial growth factor (VEGF) and the activation of telomerase. The ability of these compounds to inhibit proliferation of two tumoral cell lines (HT-29 and MCF-7) and one non tumoral cell line (HEK-293) was first determined. Subsequently, we determined the capacity of the compounds to inhibit the secretion of VEGF in the aforementioned cell lines and to downregulate the expression of the VEGF, hTERT and c-Myc genes, the two latter involved in the control of the activation of telomerase. One of the synthetic stilbenes, (E)-4-(4-methoxystyryl)aniline, showed strong cytotoxicity and proved able to cause a marked decrease both in the secretion of VEGF and in the expression of the hTERT and c-Myc genes, in all cases at concentrations in the low nanomolar range.
authors.affiliation: Depart. de Q. Inorgánica y Orgánica, Univ. Jaume I, E-12071, Castellón, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Martí-Centelles
authors.affiliation: Depart. de Q. Inorgánica y Orgánica, Univ. Jaume I, E-12071, Castellón, Spain. Electronic address: efalomir@qio.uji.es.
authors.forename: Eva
authors.initials: E
authors.lastname: Falomir
authors.affiliation: Depart. de Q. Inorgánica y Orgánica, Univ. Jaume I, E-12071, Castellón, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Murga
authors.affiliation: Depart. de Q. Inorgánica y Orgánica, Univ. Jaume I, E-12071, Castellón, Spain. Electronic address: mcarda@qio.uji.es.
authors.forename: Miguel
authors.initials: M
authors.lastname: Carda
authors.affiliation: Depart. de Q. Orgánica, Univ. de Valencia, E-46100, Burjassot, Valencia, Spain.
authors.forename: J Alberto
authors.initials: JA
authors.lastname: Marco
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects* / Q000235:genetics; D057809:HEK293 Cells; D019073:HT29 Cells; D006801:Humans; D061986:MCF-7 Cells; D015394:Molecular Structure; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D000077185:Resveratrol; D013267:Stilbenes / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity*; D013329:Structure-Activity Relationship; D019098:Telomerase / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: D016271:Proto-Oncogene Proteins c-myc; D013267:Stilbenes; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C509186:TERT protein, human; D019098:Telomerase; D000077185:Resveratrol
keywords: Gene regulation; Resveratrol; Stilbenes; Telomerase; VEGF; c-Myc; hTERT