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J Mol Neurosci (2013) 51:503513 DOI 10.1007/s12031-013-0076-7
Antiproliferative Effects of PACAP and VIP in Serum-Starved Glioma Cells
Agata Grazia DAmico & Soraya Scuderi &
Salvatore Saccone & Alessandro Castorina &
Filippo Drago & Velia DAgata
Received: 18 April 2013 /Accepted: 15 July 2013 /Published online: 31 July 2013 # Springer Science+Business Media New York 2013
Abstract Emerging evidence have suggested that calorie restriction (CR) is a reliable method to decrease cancer development since it produces changes in tumor microenvironment that interfere with cell proliferation, tissue invasion, and formation of metastases. Studies on the role of pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) in cancer cells indicate that their influence on cell growth is either cell type specific or dependent on culture conditions. Evidence showing the effect of PACAP and VIP in glioma cells grown under conditions mimicking CR are currently unavailable. Therefore, we explored the effects of both PACAP and VIP in C6 glioma cells either grown in a normal growth medium or exposed to serum starvation, to resemble an acute condition of CR. Cell viability, expression of proteins related to cell proliferation (cyclin D1), apoptosis (Bcl2, p53, and cleaved caspase-3), and cell malignancy (GFAP and nestin) were assessed by MTT assay, immunoblot, and immunolocalization, respectively. Results demonstrated that CR significantly decreased cell proliferation, reduced levels of cyclin D1 and Bcl2, and increased the expression of p53 and cleaved caspase-3. Surprisingly, all of these CR-driven effects were further exacerbated by PACAP
or VIP treatment. We also found that PACAP or VIP prevented GFAP decrease caused by CR and further reduced the expression of nestin, a prognostic marker of malignancy. In conclusion, these data demonstrate that PACAP and VIP possess antiproliferative properties against glioma cells that depend on the specific culture settings, further supporting the idea that CR might offer new avenues to improve peptide-oriented glioma cancer treatment.
Keywords Pituitary adenylate cyclase-activating polypeptide . Vasoactive intestinal peptide . Calorie restriction . Glioma cells
Introduction
Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) belong to a family of peptides which include secretine, glucagon, and peptide histi-dine isoleucine, all involved in the modulation of numerous biological functions in vertebrates (Vaudry et al. 2009; Dickson and Finlayson 2009) The biologically active form PACAP38 has...