title: Signalling pathways involved in antitumoral effects of VIP in human renal cell carcinoma A498 cells: VIP induction of p53 expression.
abstract: Vasoactive intestinal peptide (VIP) decreases cell proliferation through PI3K signalling and prevents tumour progression in clear renal cell carcinoma (RCC). Here we analyzed the signalling pathways that mediate such VIP effects by using human RCC A498 cells. The effects of treatment with 1 μM VIP and/or specific protein kinase inhibitors such as H89, Wortmannin and PD98059 were studied by cell adhesion assay, ELISA of VEGF165 and ROS production assays. Semiquantitative RT-PCR and western blot were performed to study p53 expression. VIP increased cell adhesion and ROS production, and decreased VEGF165 secretion through PI3K signalling. Moreover, VIP increased nuclear expression of tumour suppressor p53. VIP effects could be blocked by cell incubation with a specific p53 inhibitor, cyclin pifithrin-α hydrobromide (CPFT-αH). In conclusion, this study provides a p53-dependent mechanism by which VIP regulates cell proliferation in RCC development. It supports a potential usefulness of VIP in new therapies of RCC.
authors.affiliation: Department of Systems Biology, Unit of Biochemistry and Molecular Biology, University of Alcalá, 28871 Alcalá de Henares, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Vacas
authors.affiliation: Department of Systems Biology, Unit of Biochemistry and Molecular Biology, University of Alcalá, 28871 Alcalá de Henares, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Muñoz-Moreno
authors.affiliation: Department of Systems Biology, Unit of Biochemistry and Molecular Biology, University of Alcalá, 28871 Alcalá de Henares, Spain.
authors.forename: Ana B
authors.initials: AB
authors.lastname: Fernández-Martínez
authors.affiliation: Department of Systems Biology, Unit of Biochemistry and Molecular Biology, University of Alcalá, 28871 Alcalá de Henares, Spain.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Bajo
authors.affiliation: Department of Surgery and Medical and Social Sciences, Unit of Surgery, University of Alcalá, 28871 Alcalá de Henares, Spain; Department of Urology, Príncipe de Asturias Hospital, 28871 Alcalá de Henares, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Sánchez-Chapado
authors.affiliation: Department of Systems Biology, Unit of Biochemistry and Molecular Biology, University of Alcalá, 28871 Alcalá de Henares, Spain. Electronic address: juancarlos.prieto@uah.es.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Prieto
authors.affiliation: Department of Systems Biology, Unit of Biochemistry and Molecular Biology, University of Alcalá, 28871 Alcalá de Henares, Spain.
authors.forename: María J
authors.initials: MJ
authors.lastname: Carmena
mesh_terms: D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*; D014660:Vasoactive Intestinal Peptide / Q000008:administration & dosage*
chemical_list: D017382:Reactive Oxygen Species; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D014660:Vasoactive Intestinal Peptide; D000242:Cyclic AMP; D019869:Phosphatidylinositol 3-Kinases
keywords: PI3K; Renal cell carcinoma; VEGF; VIP; p53