title: Necroptosis mediates the antineoplastic effects of the soluble fraction of polysaccharide from red wine in Walker-256 tumor-bearing rats.
abstract: Polysaccharides are substances that modify the biological response to several stressors. The present study investigated the antitumor activity of the soluble fraction of polysaccharides (SFP), extracted from cabernet franc red wine, in Walker-256 tumor-bearing rats. The monosaccharide composition had a complex mixture, suggesting the presence of arabinoglactans, mannans, and pectins. Treatment with SFP (30 and 60mg/kg, oral) for 14days significantly reduced the tumor weight and volume compared with controls. Treatment with 60mg/kg SFP reduced blood monocytes and neutrophils, reduced the tumor activity of N-acetylglucosaminidase, myeloperoxidase, and nitric oxide, increased blood lymphocytes, and increased the levels of tumor necrosis factor α (TNF-α) in tumor tissue. Treatment with SFP also induced the expression of the cell necroptosis-related genes Rip1 and Rip3. The antineoplastic effect of SFP appears to be attributable to its action on the immune system by controlling the tumor microenvironment and stimulating TNF-α production, which may trigger the necroptosis pathway.
authors.affiliation: Department of Pharmacology, Federal University of Paraná, Curitiba, PR, Brazil.
authors.forename: Maria Carolina
authors.initials: MC
authors.lastname: Stipp
authors.affiliation: Department of Biochemistry and Molecular Biology, Federal University of Paraná, Curitiba, PR, Brazil.
authors.forename: Iglesias de Lacerda
authors.initials: IL
authors.lastname: Bezerra
authors.affiliation: Department of Pharmacology, Federal University of Paraná, Curitiba, PR, Brazil.
authors.forename: Claudia Rita
authors.initials: CR
authors.lastname: Corso
authors.affiliation: Department of Pharmacology, Federal University of Paraná, Curitiba, PR, Brazil.
authors.forename: Francislaine A
authors.initials: FA
authors.lastname: Dos Reis Livero
authors.affiliation: Department of Pharmacology, Federal University of Paraná, Curitiba, PR, Brazil.
authors.forename: Luiz Alexandre
authors.initials: LA
authors.lastname: Lomba
authors.affiliation: Department of Biochemistry and Molecular Biology, Federal University of Paraná, Curitiba, PR, Brazil.
authors.forename: Adriana Rute Cordeiro
authors.initials: AR
authors.lastname: Caillot
authors.affiliation: Department of Pharmacology, Federal University of Paraná, Curitiba, PR, Brazil.
authors.forename: Aleksander Roberto
authors.initials: AR
authors.lastname: Zampronio
authors.affiliation: Department of Medical Pathology, Federal University of Paraná, Curitiba, PR, Brazil.
authors.forename: José Ederaldo
authors.initials: JE
authors.lastname: Queiroz-Telles
authors.affiliation: Department of Basic Pathology, Federal University of Paraná, Curitiba, PR, Brazil.
authors.forename: Giseli
authors.initials: G
authors.lastname: Klassen
authors.affiliation: Department of Basic Pathology, Federal University of Paraná, Curitiba, PR, Brazil.
authors.forename: Edneia A S
authors.initials: EA
authors.lastname: Ramos
authors.affiliation: Department of Biochemistry and Molecular Biology, Federal University of Paraná, Curitiba, PR, Brazil.
authors.forename: Guilherme Lanzi
authors.initials: GL
authors.lastname: Sassaki
authors.affiliation: Department of Pharmacology, Federal University of Paraná, Curitiba, PR, Brazil. Electronic address: aleacco@ufpr.br.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Acco
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D011134:Polysaccharides / Q000737:chemistry / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014920:Wine
chemical_list: D000970:Antineoplastic Agents; D011134:Polysaccharides; D014409:Tumor Necrosis Factor-alpha; D017346:Protein Serine-Threonine Kinases; C586536:RIPK1 protein, rat; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; C582791:Ripk3 protein, rat
keywords: Griess solution (0.1% N-1-naphthyl-tilediamine, 1% sulfanilamide in 5% H(3)PO(4)); N-acetyl-β-d-glucosamine; TriZol Reagent; Walker-256 tumor; buffered 10% formalin; cabernet franc; dimethylformamide 8%; eTrypan blue, 2 M trifluoroacetic acid; ethanol; ethylenediaminetetraacetic acid (EDTA) (0.5 M, pH 8.0); hematoxylin and eosin (HE); immunomodulation; ketamine hydrochloride; metothrexate; necroptosis; p-nitrofen; p-nitrophenyl-N-acetyl-β-d-glucosamine; paraffin; phosphate buffer (pH 6.5); phosphate buffered saline (PBS, 16.5 mM phosphate, 137 mM NaCl, and 2.7 mM KCl) at pH 7.4; polysaccharide; red wine; saline Triton X-100 0.1%, TMB 18.4 mM; sodium acetate (NaOAc); xylazine hydrochloride;; xylol