title: Antiproliferative effects of PACAP and VIP in serum-starved glioma cells.
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.
authors.affiliation: Section of Anatomy and Histology, Department of Bio-Medical Sciences, University of Catania, Via S.Sofia, 87, 95123, Catania, Italy.
authors.forename: Agata Grazia
authors.initials: AG
authors.lastname: D'Amico
authors.forename: Soraya
authors.initials: S
authors.lastname: Scuderi
authors.forename: Salvatore
authors.initials: S
authors.lastname: Saccone
authors.forename: Alessandro
authors.initials: A
authors.lastname: Castorina
authors.forename: Filippo
authors.initials: F
authors.lastname: Drago
authors.forename: Velia
authors.initials: V
authors.lastname: D'Agata
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D016895:Culture Media, Serum-Free / Q000494:pharmacology*; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D005910:Glioma / Q000378:metabolism; D064231:Nestin / Q000235:genetics / Q000378:metabolism; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000494:pharmacology*; D051381:Rats; D014158:Transcription, Genetic / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
chemical_list: D051017:Apoptosis Regulatory Proteins; D016895:Culture Media, Serum-Free; D005904:Glial Fibrillary Acidic Protein; D064231:Nestin; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1; D014660:Vasoactive Intestinal Peptide
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