title: Influence of bioactive sulfated polysaccharide-protein complexes on hepatocarcinogenesis, angiogenesis and immunomodulatory activities.
abstract: To explore the in vivo anticancer, anti-angiogenesis and immunomodulatory efficacies of the bioactive polysaccharide isolated from cold aqueous extract of Jania rubens (JCEM) and Pterocladia capillacea (PCEM) as well as hot aqueous extract of Enteromorpha intestinalis (EHEM) against hepatocellular carcinoma rat model (HCC) and to study their chemical composition.
  
  
  
  The sugars and amino acids composition of the bioactive polysaccharides of JCEM, PCEM and EHEM were determined using gas liquid chromatography and amino acid analyzer, respectively. These polysaccharide extracts (20 mg/kg b.wt. for 5 weeks) were assessed on hepatocarcinogenesis in rats and α-fetoprotein (AFP), carcinoembryonic antigen (CEA), glypican-3 (GPC-3), hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) and Ig G levels were evaluated.
  
  
  
  The GLC analysis of JCEM, PCEM and EHEM polysaccharide revealed the presence of 10, 9 and 10 sugars, in addition the amino acid analyzer enable identification of 16, 15 and 15 amino acids, respectively. These polysaccharide extracts of JCEM, PCEM and EHEM produced significant decrease in serum AFP, CEA, GPC-3, HGF and VEGF compared with untreated HCC group. JCEM, PCEM and EHEM had an immunostimulatory responses by increasing the IgG levels as compared by naïve value (1.23, 1.53 and 1.17 folds), respectively. The bioactive polysaccharides in HCC induced rats improved the humoral immune response. The photomicrographs of liver tissue sections of the groups of HCC treated with polysaccharide extracts of Jania rubens and Enteromorpha intestinalis showed intact histological structure. Moreover, fractions HE1, HE4, HE7 obtained from polysaccharide of EHEM showed moderate cytotoxic activity against HepG2 in vitro with IC5073.1, 42.6, 76.2 μg/mL. However, fractions of PCEM and JCEM show no or weak cytotoxicity against HepG2 in vitro where the cytotoxic activity of their crude polysaccharide extract proved synergetic effect.
  
  
  
  The pronounced antitumor activity of sulfated polysaccharide-protein complexes of JCEM and EHEM is due to direct cytotoxic activity, anti-hepatocarcinogenesis, and anti-angiogenesis. In addition, JCEM, PCEM and EHEM had an immunostimulatory response and improved the humoral immune response in HCC induced rats.
authors.affiliation: Pharmacognosy Department, National Research Centre, Dokki, Giza, Egypt. Electronic address: matlouba2002@hotmail.com.
authors.forename: Azza A
authors.initials: AA
authors.lastname: Matloub
authors.affiliation: Hormones Department, National Research Centre, Dokki, Giza, Egypt.
authors.forename: Hadeer A
authors.initials: HA
authors.lastname: Aglan
authors.affiliation: Chemistry of Natural Compounds Department, National Research Centre, Dokki, Giza, Egypt.
authors.forename: Sahar Salah
authors.initials: SS
authors.lastname: Mohamed El Souda
authors.affiliation: Medicinal and Pharmaceutical Chemistry Department (Pharmacology Group), National Research Centre, Dokki, Giza, Egypt.
authors.forename: Mona Elsayed
authors.initials: ME
authors.lastname: Aboutabl
authors.affiliation: Therapeutical Chemistry Department, National Research Centre, Dokki, Giza, Egypt; Laboratory of Immune and Biomarkers for Infection, The Center of Excellence for Advanced Sciences, National Research Centre, Dokki, Giza, Egypt.
authors.forename: Amany Sayed
authors.initials: AS
authors.lastname: Maghraby
authors.affiliation: Hormones Department, National Research Centre, Dokki, Giza, Egypt.
authors.forename: Hanaa H
authors.initials: HH
authors.lastname: Ahmed
keywords: Anti-angiogenesis; Anti-tumor activity; Enteromorpha intestinalis; Jania rubens; Polysaccharide-protein complexes; Pterocladia capillacea