Low molecular weight mannogalactofucans (LMMGFs) prepared by enzymatic degradation of high molecular weight Undaria galactofucan (MF) were evaluated for their anti-cancer effects against human prostate cancer. Correlation NMR and linkage analyses confirmed that LMMGFs consist mainly of α-fucose and β-galactose units: α-fucose units are 1,3-linked; β-galactose units are terminal, 1,3- and/or 1,6-linked; both sugars are partially sulphated, fucose at positions O-2 and/or O-4 and galactose at O-3. Mannose residue, as a minor sugar, presents as the 1,4-linked terminal units. LMMGFs more significantly induced cell cycle arrest at the G0/G1 phase and cell death via suppression of the Akt/GSK-3β/β-catenin pathway than MF in human PC-3 prostate cancer cells. LMMGFs upregulated mRNA expression of death receptor-5 (DR-5), the ratio of Bax to Bcl-2, the cleavage of caspases and PARP, the depolarisation of mitochondrial membrane potential, and ROS generation. LMMGFs (200-400 mg/kg) effectively reduced both tumour volume and size in a xenografted mouse model. These results demonstrated that LMMGFs attenuate the growth of human prostate cancer cells both in vitro and in vivo, suggesting that LMMGFs can be used as a potent functional ingredient in health-beneficial foods or as a therapeutic agent to prevent or treat androgen-independent human prostate cancer. Graphical Abstract.
- MeSH
- apoptóza účinky léků MeSH
- beta-katenin metabolismus MeSH
- GSK3B metabolismus MeSH
- kontrolní body buněčného cyklu účinky léků MeSH
- lidé MeSH
- membránový potenciál mitochondrií účinky léků MeSH
- messenger RNA genetika MeSH
- molekulová hmotnost MeSH
- myši MeSH
- nádory prostaty farmakoterapie metabolismus MeSH
- polysacharidy chemie farmakologie terapeutické užití MeSH
- Undaria chemie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Low-molecular-weight mannogalactofucans (LMMGFs, <4000g/mol) were prepared by the enzymatic degradation of Undaria pinnatifida sporophyll galactofucan (MF) and evaluated or their antiviral activities and underlying action mechanisms against herpes simplex virus type 1 (HSV-1). The 50% inhibitory concentrations (IC50) of LMMGFs and MF were 2.64 and 2.42μg/mL, respectively. LMMGFs inhibited the viral entry on the host cell surface and also exhibited inhibitory activity directly against viral particles, as observed in a virucidal assay. LMMGFs dose-dependently enhanced the mRNA expression of Toll-like receptor 2 (TLR2) and stimulated the phosphorylation of Akt and JNK in Vero cells. These results clearly demonstrated that LMMGFs use TLR2 as their receptor, preventing HSV-1 infection on the host cell surface and antagonizing viral adsorption via TLR2 pathway activation in Vero cells.
- MeSH
- antivirové látky chemie farmakologie MeSH
- Cercopithecus aethiops MeSH
- galaktosa chemie farmakologie MeSH
- herpes simplex metabolismus prevence a kontrola MeSH
- lidský herpesvirus 1 účinky léků MeSH
- molekulová hmotnost MeSH
- rozpustnost MeSH
- toll-like receptor 2 metabolismus MeSH
- Vero buňky MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Previously, we reported that the sulphated polysaccharides (SPS)-CF, a water-soluble polysaccharide isolated and purified from Korean green alga Maesaengi (Capsosiphon fulvescens, Chlorophyta), is a glucuronogalactomannan based mainly on the monosaccharide composition determined by high-performance liquid chromatography (HPLC) analysis after 1-phenyl-3-methyl-5-pyrazolone (PMP) labelling of sugars in the acid (trifluoroacetic acid (TFA)) hydrolyzates of SPS-CF, which showed mannose (55.4 mol %), galactose (25.3 mol %) and glucuronic acid (16.3 mol %) as major sugars (Na et al., Int Immunopharmacol 10:364-370, 2010). However, the results of the present study re-performed for monosaccharide composition of this polysaccharide using, in addition to HPLC of PMP-labelled sugars, other separation methods, i.e. high-performance anion-exchange chromatography with pulsed amperometric detection (HPAEC-PAD), gas chromatography with flame ionising detection (GC-FID) and thin-layer chromatography (TLC), clearly demonstrated that the most prominent neutral monosaccharides of SPS-CF are xylose (38.6-49.4 mol %) and rhamnose (39.6-45 mol %), while mannose and galactose are present at a much lesser extent or in negligible amount. These extensive monosaccharide analyses, correlation nuclear magnetic resonance (NMR), electrospray ionization mass spectrometry (ESI-MS) and matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) measurements confirmed the sulphated glucuronorhamnoxylan (ulvan) type of SPS-CF polysaccharide, whose backbone is composed of alternating sequence of 4-linked L-rhamnose-3-sulphate and D-xylose residues (ulvobiose U3s) carrying monomeric D-glucuronic acid or D-glucuronic acid-3-sulphate on O-2 of some L-rhamnose-3-sulphate units as the side chains. The SPS-CF exhibited significant in vitro anti-coagulant activity by which the activated partial thromboplastin time (aPTT) and thrombin time (TT) were significantly prolonged. The results of this study demonstrated that the ulvan SPS-CF isolated from Korean Maesaengi C. fulvescens can be considered a potential anti-coagulant agent.
- MeSH
- antikoagulancia chemie izolace a purifikace farmakologie MeSH
- Chlorophyta metabolismus MeSH
- chromatografie na tenké vrstvě MeSH
- chromatografie plynová MeSH
- lidé MeSH
- magnetická rezonanční spektroskopie MeSH
- mannany chemie izolace a purifikace farmakologie MeSH
- monosacharidy analýza MeSH
- parciální tromboplastinový čas MeSH
- plamínková ionizace MeSH
- spektrometrie hmotnostní - ionizace laserem za účasti matrice MeSH
- trombinový čas MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
