RESUMEN

The proximal promoter region of the human vascular endothelial growth factor (VEGF) gene contains a guanine-rich strand that can act as a transcriptional silencer by forming an intramolecular G-quadruplex. In this study, we compared two perylene monoimide derivatives, PM1 and PM2, with the well-studied perylene diimide derivative, PIPER, and the well-studied porphyrin derivative, TmPyP(4), with regard to G-quadruplex formation, G-quadruplex binding selectivity, and human VEGF gene silencing in A549 lung cancer cells. The results show that these perylene derivatives can preferentially induce intramolecular G-quadruplex formation from a duplex containing the VEGF G-quadruplex motif in vitro. Incubating A549 lung cancer cells with these perylene derivatives, especially PM2, led to the reduction of both VEGF mRNA and VEGF protein. This study might provide the foundation for the rational design and development of new perylene derivatives as effective anti-angiogenesis agents for cancer therapy.

Asunto(s)

Perfilación de la Expresión Génica , Regulación de la Expresión Génica/efectos de los fármacos , Imidas/química , Perileno/análogos & derivados , Factor A de Crecimiento Endotelial Vascular/biosíntesis , Inhibidores de la Angiogénesis/farmacología , Antineoplásicos/farmacología , Línea Celular Tumoral , Relación Dosis-Respuesta a Droga , Regulación hacia Abajo , Diseño de Fármacos , G-Cuádruplex , Silenciador del Gen , Células HeLa , Humanos , Imidas/farmacología , Modelos Biológicos , Modelos Químicos , Perileno/química , Perileno/farmacología , Reacción en Cadena de la Polimerasa/métodos , ARN Mensajero/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo