title: Effects of a novel cyclic RGD peptidomimetic on cell proliferation, migration and angiogenic activity in human endothelial cells.
abstract: BACKGROUND
  Cyclic RGD peptidomimetics containing a bifunctional diketopiperazine scaffold are a novel class of high-affinity ligands for the integrins αVβ3 and αVβ5. Since integrins are a promising target for the modulation of normal and pathological angiogenesis, the present study aimed at characterizing the ability of the RGD peptidomimetic cyclo[DKP-RGD] 1 proliferation, migration and network formation in human umbilical vein endothelial cells (HUVEC).
  
  
  METHODS
  Cell viability was assessed by flow cytometry and annexin V (ANX)/propidium iodide (PI) staining. Cell proliferation was evaluated by the ELISA measurement of bromodeoxyuridine (BrdU) incorporation. Network formation by HUVEC cultured in Matrigel-coated plates was evaluated by optical microscopy and image analysis. Integrin subunit mRNA expression was assessed by real time-PCR and Akt phosphorylation by western blot analysis.
  
  
  RESULTS
  Cyclo[DKP-RGD] 1 does not affect cell viability and proliferation either in resting conditions or in the presence of the pro-angiogenic growth factors VEGF, EGF, FGF, and IGF-I. Addition of cyclo[DKP-RGD] 1 however significantly decreased network formation induced by pro-angiogenic growth factors or by IL-8. Cyclo[DKP-RGD] 1 did not affect mRNA levels of αV, β3 or β5 integrin subunits, however it significantly reduced the phosphorylation of Akt.
  
  
  CONCLUSIONS
  Cyclo[DKP-RGD] 1 can be a potential modulator of angiogenesis induced by different growth factors, possibly devoid of the adverse effects of cytotoxic RGD peptidomimetic analogues.
authors: Department of Science and High Technology, University of Insubria, Como, Italy.
authors: Roberto
authors: R
authors: Fanelli
authors: Center for Research in Medical Pharmacology, University of Insubria, Via Ottorino Rossi n. 9 21100, Varese, VA, Italy.
authors: Laura
authors: L
authors: Schembri
authors: Department of Science and High Technology, University of Insubria, Como, Italy.
authors: Umberto
authors: U
authors: Piarulli
authors: Center for Research in Medical Pharmacology, University of Insubria, Via Ottorino Rossi n. 9 21100, Varese, VA, Italy.
authors: Monica
authors: M
authors: Pinoli
authors: Center for Research in Medical Pharmacology, University of Insubria, Via Ottorino Rossi n. 9 21100, Varese, VA, Italy.
authors: Emanuela
authors: E
authors: Rasini
authors: Department of Drug Sciences, University of Pavia, Pavia, Italy.
authors: Mayra
authors: M
authors: Paolillo
authors: Department of Drug Sciences, University of Pavia, Pavia, Italy.
authors: Marisa Carlotta
authors: MC
authors: Galiazzo
authors: Center for Research in Medical Pharmacology, University of Insubria, Via Ottorino Rossi n. 9 21100, Varese, VA, Italy.
authors: Marco
authors: M
authors: Cosentino
authors: Center for Research in Medical Pharmacology, University of Insubria, Via Ottorino Rossi n. 9 21100, Varese, VA, Italy.
authors: Franca
authors: F
authors: Marino
keywords: Angiogenesis; Human umbilical vein endothelial cells; Integrins; Interleukin-8; RGD peptidomimetics