RESUMEN
Hepatocellular carcinoma (HCC) is an aggressive tumor triggered by various factors such as virus infection and alcohol abuse. Glucuronomannan polysaccharide (Gx) is a subtype of fucoidans that possesses many bioactivities, but its anti-tumor activities in HCC have not been reported. In this paper, the anti-tumor effects of glucuronomannan oligosaccharides (Gx) and its sulfated derivatives (GxSy) on hepatocarcinoma Huh7.5 cells were investigated. The anti-proliferation, anti-metastasis activities, and underlying mechanism of Gx and GxSy on Huh7.5 cells were analyzed and compared by MTT, wound healing, transwell, and western blotting assays, respectively. Results showed that the best anti-proliferation effects were G4S1 and G4S2 among 13 drugs, which were 38.67% and 30.14%, respectively. The cell migration rates were significantly inhibited by G2S1, G4S2, G6S2, and unsulfated Gn. In addition, cell invasion effects treated with G4S1, G4S2, and G6S1 decreased to 48.62%, 36.26%, and 42.86%, respectively. Furthermore, sulfated G4 regulated the expression of (p-) FAK and MAPK pathway, and sulfated G6 down-regulated the MAPK signaling pathway while activating the PI3K/AKT pathway. On the contrary, sulfated G2 and unsulfated Gx had no inhibited effects on the FAK-mTOR pathway. These results indicated that sulfated Gx derivatives have better anti-tumor activities than unsulfated Gx in cell proliferation and metastasis process in vitro, and those properties depend on the sulfation group levels. Moreover, degrees of polymerization of Gx also played a vital role in mechanisms and bioactivities. This finding shows the structure-activity relationship for developing and applying the marine oligosaccharide candidates.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Línea Celular Tumoral , Sulfatos/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Oligosacáridos/farmacología , Proliferación Celular , Movimiento Celular , Proteínas Proto-Oncogénicas c-akt/metabolismoRESUMEN
Parkinson's disease (PD), characterized by dopaminergic neuron degeneration in the substantia nigra and dopamine depletion in the striatum, affects up to 1% of the global population over 50 years of age. Our previous study found that a heteropolysaccharide from Saccharina japonica exhibits neuroprotective effects through antioxidative stress. In view of its high molecular weight and complex structure, we degraded the polysaccharide and subsequently obtained four oligosaccharides. In this study, we aimed to further detect the neuroprotective mechanism of the oligosaccharides. We applied MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) to induce PD, and glucuronomannan oligosaccharides (GMn) was subsequently administered. Results showed that GMn ameliorated behavioral deficits in Parkinsonism mice. Furthermore, we observed that glucuronomannan oligosaccharides contributed to down-regulating the apoptotic signaling pathway through enhancing the expression of tyrosine hydroxylase (TH) in dopaminergic neurons. These results suggest that glucuronomannan oligosaccharides protect dopaminergic neurons from apoptosis in PD mice.
Asunto(s)
Antiparkinsonianos/farmacología , Apoptosis/efectos de los fármacos , Encéfalo/efectos de los fármacos , Neuronas Dopaminérgicas/efectos de los fármacos , Glucuronatos/farmacología , Manosa/análogos & derivados , Oligosacáridos/farmacología , Trastornos Parkinsonianos/prevención & control , Algas Marinas , 1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina , Animales , Antiparkinsonianos/aislamiento & purificación , Proteínas Reguladoras de la Apoptosis/metabolismo , Conducta Animal/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/patología , Encéfalo/fisiopatología , Modelos Animales de Enfermedad , Neuronas Dopaminérgicas/metabolismo , Neuronas Dopaminérgicas/patología , Glucuronatos/aislamiento & purificación , Masculino , Manosa/aislamiento & purificación , Manosa/farmacología , Ratones Endogámicos C57BL , Actividad Motora/efectos de los fármacos , Oligosacáridos/aislamiento & purificación , Prueba de Campo Abierto/efectos de los fármacos , Trastornos Parkinsonianos/inducido químicamente , Trastornos Parkinsonianos/metabolismo , Trastornos Parkinsonianos/patología , Algas Marinas/química , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
Glucuronomannan oligosaccharides (Gs) were derived from fucoidan, which was extracted from the brown alga Sargassum thunbergii. Sulfated glucuronomannan oligosaccharides (SGs) were obtained by the sulfation of Gs. NMR techniques were used to reveal that the order of sulfation was Man-C6 > Man-C4 > Man-C1R > GlcA-C3 > Man-C3 > GlcA-C2. Finally, the antioxidant activities (hydroxyl radical scavenging activity, superoxide radical scavenging activity, reducing power and DPPH radical scavenging activity) of Gs and SGs were determined. The findings showed that the higher the degree of polymerization, the better the activity, except for the hydroxyl radical scavenging activity. In addition, the higher the sulfate content, the lower the activities for the reducing power and DPPH radical scavenging activity. Opposite results were found for the superoxide radical scavenging activity. Finally, compared with fucoidan, most Gs and SGs had higher antioxidant activity, suggesting that they might be good candidates for antioxidants.