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1.
Int J Mol Sci ; 23(14)2022 Jul 11.
Article in English | MEDLINE | ID: mdl-35886983

ABSTRACT

Melanoma is a highly metastatic and rapidly progressing cancer, a leading cause of mortality among skin cancers. The melanoma microenvironment, formed from the activity of malignant cells on the extracellular matrix and the recruitment of immune cells, plays an active role in the development of drug resistance and tumor recurrence, which are clinical challenges in cancer treatment. These tumoral metabolic processes are affected by proteins, including Galectin-3 (Gal-3), which is extensively involved in cancer development. Previously, we characterized a partially methylated mannogalactan (MG-Pe) with antimelanoma activities. In vivo models of melanoma were used to observe MG-Pe effects in survival, spontaneous, and experimental metastases and in tissue oxidative stress. Analytical assays for the molecular interaction of MG-Pe and Gal-3 were performed using a quartz crystal microbalance, atomic force microscopy, and contact angle tensiometer. MG-Pe exhibits an additive effect when administered together with the chemotherapeutic agent dacarbazine, leading to increased survival of treated mice, metastases reduction, and the modulation of oxidative stress. MG-Pe binds to galectin-3. Furthermore, MG-Pe antitumor effects were substantially reduced in Gal-3/KO mice. Our results showed that the novel Gal-3 ligand, MG-Pe, has both antitumor and antimetastatic effects, alone or in combination with chemotherapy.


Subject(s)
Antineoplastic Agents , Galectin 3 , Melanoma , Skin Neoplasms , Animals , Antineoplastic Agents/metabolism , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Dacarbazine/metabolism , Dacarbazine/pharmacology , Dacarbazine/therapeutic use , Galectin 3/metabolism , Galectin 3/pharmacology , Galectin 3/therapeutic use , Ligands , Melanoma/drug therapy , Melanoma/metabolism , Mice , Neoplasm Recurrence, Local , Skin Neoplasms/drug therapy , Skin Neoplasms/metabolism , Tumor Microenvironment/drug effects , Tumor Microenvironment/physiology
2.
Carbohydr Polym ; 289: 119436, 2022 Aug 01.
Article in English | MEDLINE | ID: mdl-35483849

ABSTRACT

Polysaccharides from seaweed have been shown to present a variety of antitumor effects, however the understanding of which structural patterns are responsible for these biological effects are still unclear. This review aimed to gather and critically evaluate published data of seaweed polysaccharide's chemical structure elucidation and their relation with antimelanoma effects. Data were collected at the electronic article databases Science Direct, NCBI/Pubmed and Google Scholar, selecting papers with polysaccharide structural information and biological effects on melanoma models. Most of the papers referred to sulfated polysaccharides as fucans and fucoidans, and to a lesser extent galactans, rhamnans, alginates, and neutral one's glucans. Fine chemical features as presence and position of sulfate groups, monosaccharide composition, linear or branched backbones, and glycosidic linkage type are crucial to antimelanoma effects, as well as molecular weight and macromolecular conformation.


Subject(s)
Seaweed , Sulfates , Galactans/chemistry , Polysaccharides/chemistry , Polysaccharides/pharmacology , Sulfur Oxides , Vegetables
3.
Int J Biol Macromol ; 185: 551-561, 2021 Aug 31.
Article in English | MEDLINE | ID: mdl-34216657

ABSTRACT

Advanced melanoma patients that are not included in common genetic classificatory groups lack effective and safe therapeutic options. Chemotherapy and immunotherapy show unsatisfactory results and devastating adverse effects for these called triple wild-type patients. New approaches exploring the intrinsic antitumor properties of gold nanoparticles might reverse this scenario as a safer and more effective alternative. Therefore, we investigated the efficacy and safety of a composite made of gum arabic-functionalized gold nanorods (GA-AuNRs) against triple wild-type melanoma. The natural polymer gum arabic successfully stabilized the nanorods in the biological environment and was essential to improve their biocompatibility. In vivo results obtained from treating triple wild-type melanoma-bearing mice showed that GA-AuNRs remarkably reduced primary tumor growth by 45%. Furthermore, GA-AuNRs induced tumor histological features associated with better prognosis while also reducing superficial lung metastasis depth and the incidence of intrapulmonary metastasis. GA-AuNRs' efficacy comes from their capacity to reduce melanoma cells ability to invade the extracellular matrix and grow into colonies, in addition to a likely immunomodulatory effect induced by gum arabic. Additionally, a broad safety investigation found no evidence of adverse effects after GA-AuNRs treatment. Therefore, this study unprecedentedly reports GA-AuNRs as a potential nanomedicine for advanced triple wild-type melanomas.


Subject(s)
Gold/administration & dosage , Gum Arabic/chemistry , Lung Neoplasms/drug therapy , Lung Neoplasms/secondary , Melanoma/drug therapy , Animals , BALB 3T3 Cells , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Extracellular Matrix/metabolism , Gold/chemistry , Gold/pharmacology , Humans , Lung Neoplasms/metabolism , Melanoma/metabolism , Metal Nanoparticles , Mice , Treatment Outcome , Xenograft Model Antitumor Assays
4.
Phytochemistry ; 65(16): 2347-55, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15381006

ABSTRACT

The polysaccharide isolated from the gum exudate of palm Scheelea phalerata (SPN) was water-insoluble and composed of Fuc, Ara, Xyl, and uronic acid moieties in a 5:34:54:7 molar ratio: 12% of phenolics were also present. A soluble polysaccharide (SPNa) was obtained after alkaline treatment, which contained Fuc, Ara, Xyl and uronic acid in a 7:44:42:7 molar ratio, with only 2% phenolics. SPNa had an M(W) approximately 1.04 x 10(5) g mol(-1) and was almost monodisperse (M(W)/M(N) : 1.25 +/-0.22). It had a branched structure with side chains of 2-O-substituted Xylp (approximately 8%) and 3-O-substituted Araf (12%) units, and a large proportion of nonreducing end-units of Araf (15%), Fucp (10%), Xylp (4%), and Arap (6%). The (1 --> 4)-linked beta-Xylp main-chain units were 3-O- (9%), 2-O- (13%), and 2,3-di-O- (13%) substituted. Its (13)C NMR spectrum contained at least 9 C-1 signals, those at delta 108.6 and 107.7 arising from alpha-Araf units. Others were present at delta 175.4 from C-6 of alpha-GlcpA and delta 15.6 from C-6 of Fucp units. The main chain of SPNa was confirmed by analysis of a Smith-degraded polysaccharide (SPDS): methylation analysis provided a 2,3-Me(2)-Xyl (65%) derivative and its (13)C NMR spectrum showed five main signals typical of a (1 --> 4)-linked beta-Xylp units. Methylation analysis of a carboxy-reduced polysaccharide (SPN-CR) revealed a 2,3,4,6-Me(4)-Glc derivative (4%) arising from nonreducing end-units of GlcpA. Alpha-GlcpA-(1 --> 2)-alphabeta-Xy1p and alpha-GlcpA-(1 --> 2)-beta-Xylp-(1 --> 4)-alphabeta-Xylp were obtained via partial acid hydrolysis of SPN, showing the structure of side-chain substituents on O-2 of the main-chain units.


Subject(s)
Arecaceae/chemistry , Gingiva/chemistry , Plants, Medicinal/chemistry , Xylans/chemistry , Arabinose/analysis , Fucose/analysis , Magnetic Resonance Spectroscopy , Methylation , Polysaccharides/chemistry , Polysaccharides/isolation & purification , Uronic Acids/analysis , Xylans/analysis , Xylans/classification , Xylans/isolation & purification , Xylose/analysis
5.
Carbohydr Res ; 338(18): 1843-50, 2003 Sep 01.
Article in English | MEDLINE | ID: mdl-12932367

ABSTRACT

Structural features of the acidic, highly substituted glycanoxylan (LCP; 87% yield) from the gum exudate of the palm, Livistona chinensis, family Arecaceae, were determined. It had [alpha]D -30 degrees, Mw 1.9x10(5) and a polydispersity ratio Mw/Mn of approximately 1.0. Acid hydrolysis gave rise to Rha, Fuc, Ara, Xyl, and Gal, in a 1:6:46:44:3 molar ratio, and 12% of uronic acid was present. LCP had a highly branched structure with side-chains containing nonreducing end-units (% values are approximate) of Araf (15%), Fucp (4%), Xylp (7%), GlcpA, and 4-Me-GlcpA, and internal 2-O- (5%) and 3-O-substituted Araf (8%), and 2-O-substituted Xylp (14%) units. The (1-->4)-linked beta-Xylp main-chain units of LCP were substituted at O-3 (4%), O-2 (17%), and O-2,3 (16%). Partial acid hydrolysis gave 4-Me-alpha-GlcpA-(1-->2)-[beta-Xylp-(1-->4)](0-2)-Xyl, identified by showing that the uronic acids were single-unit side-chain substituents on O-2. Milder hydrolysis conditions removed from O-3 other side-chains containing Fucp and Araf nonreducing end-units and internal Arap, and 2-O- and 3-O-substituted Araf units. Carboxyl-reduced LCP contained 4-O-methylglucose and glucose in a 3.2:1 molar ratio, arising from GlcpA and 4-OMe-GlcpA nonreducing end-units, respectively. The gum contained small amounts of free alpha-Fucp-(1-->2)-Ara, which corresponds to structures in the polysaccharide. Free myo- and D- or L-chiro-inositol were present in a 9:1 ratio.


Subject(s)
Arecaceae/chemistry , Oligosaccharides, Branched-Chain/chemistry , Polysaccharides/chemistry , Xylans/chemistry , Arabinose/analysis , Carbohydrate Sequence , Classification , Fucose/analysis , Galactose/analysis , Gas Chromatography-Mass Spectrometry , Glucose/analysis , Glucuronates/analysis , Glucuronic Acid/analysis , Hydrolysis , Inositol/analysis , Magnetic Resonance Spectroscopy , Methylation , Molecular Sequence Data , Molecular Weight , Polysaccharides/isolation & purification , Rhamnose/analysis , Scattering, Radiation , Spectrometry, Mass, Electrospray Ionization , Uronic Acids/analysis , Xylans/analysis , Xylans/classification , Xylans/isolation & purification , Xylose/analysis
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