Necroptosis mediates the antineoplastic effects of the soluble fraction of polysaccharide from red wine in Walker-256 tumor-bearing rats

•Soluble fraction of polysaccharide extracted from cabernet franc wine has a complex mixture, with arabinogalactans, mannans and rhamnogalacturonans.•Soluble fraction of polysaccharide showed and expressive antineoplastic effects against the Walker-256 tumor in rats.•Soluble fraction of polysacchari...

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Published in:	Carbohydrate polymers Vol. 160; pp. 123 - 133
Main Authors:	Stipp, Maria Carolina, Bezerra, Iglesias de Lacerda, Corso, Claudia Rita, dos Reis Livero, Francislaine A., Lomba, Luiz Alexandre, Caillot, Adriana Rute Cordeiro, Zampronio, Aleksander Roberto, Queiroz-Telles, José Ederaldo, Klassen, Giseli, Ramos, Edneia A.S., Sassaki, Guilherme Lanzi, Acco, Alexandra
Format:	Journal Article
Language:	English
Published:	England Elsevier Ltd 15.03.2017
Subjects:	Animals antineoplastic activity Antineoplastic Agents - chemistry Antineoplastic Agents - pharmacology Apoptosis buffered 10% formalin cabernet franc dimethylformamide 8 ethanol ethylenediaminetetraacetic acid (EDTA) (0.5 M, pH 8.0) eTrypan blue, 2 M trifluoroacetic acid genes Griess solution (0.1% N-1-naphthyl-tilediamine, 1% sulfanilamide in 5% H3PO4) hematoxylin and eosin (HE) immunomodulation ketamine hydrochloride lymphocytes mannans metothrexate monocytes myeloperoxidase N-acetyl-β-d-glucosamine necroptosis Neoplasms, Experimental - drug therapy neutrophils nitric oxide p-nitrofen p-nitrophenyl-N-acetyl-β-d-glucosamine paraffin pectins 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 Polysaccharides - chemistry Polysaccharides - pharmacology Protein Serine-Threonine Kinases - metabolism Rats Receptor-Interacting Protein Serine-Threonine Kinases - metabolism red wine red wines saline Triton X-100 0.1%, TMB 18.4 mM sodium acetate (NaOAc) TriZol Reagent tumor necrosis factor-alpha Tumor Necrosis Factor-alpha - metabolism Walker-256 tumor Wine xylazine hydrochloride xylol red wine polysaccharide phosphate buffer (pH 6.5) ALT Walker-256 tumor buffered 10% formalin paraffin MPO ketamine hydrochloride p53 MTX NF-κB saline Triton X-100 0.1%, TMB 18.4 mM necroptosis p-nitrophenyl-N-acetyl-β-d-glucosamine Gapdh cabernet franc p-nitrofen ROS hematoxylin and eosin (HE) Bcl-2 NO immunomodulation dimethylformamide 8 Mlkl Vegf mRNA phosphate buffered saline (PBS, 16.5 mM phosphate, 137 mM NaCl, and 2.7 mM KCl) at pH 7.4 ethanol N-acetyl-β-d-glucosamine ANOVA xylazine hydrochloride FADD SFP TriZol Reagent AST metothrexate NaOAc Griess solution (0.1% N-1-naphthyl-tilediamine, 1% sulfanilamide in 5% H3PO4) TMB Rip-1 Rip-3 eTrypan blue, 2 M trifluoroacetic acid TNF-α NAG DNA ethylenediaminetetraacetic acid (EDTA) (0.5 M, pH 8.0) Bax xylol sodium acetate (NaOAc) HE Griess solution (0.1% N-1-naphthyl-tilediamine, 1% sulfanilamide in 5% HPO)
ISSN:	0144-8617, 1879-1344
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Summary:	•Soluble fraction of polysaccharide extracted from cabernet franc wine has a complex mixture, with arabinogalactans, mannans and rhamnogalacturonans.•Soluble fraction of polysaccharide showed and expressive antineoplastic effects against the Walker-256 tumor in rats.•Soluble fraction of polysaccharide increased the tumor TNF-α production and activated the necroptosis pathway.•Soluble fraction of polysaccharide may be a potential therapy for cancers that are modulated by immune/inflammatory processes. 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0144-8617 1879-1344
DOI:	10.1016/j.carbpol.2016.12.047