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1.
Mar Drugs ; 21(9)2023 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-37755099

RESUMO

This work reports the detailed structure of fucoidan from Sargassum miticum (2SmF2) and its ability to potentiate the inhibitory effect of glycolysis inhibitor 2-deoxy-d-glucose (2-DG). 2SmF2 was shown to be sulfated and acetylated galactofucan containing a main chain of alternating residues of 1,3- and 1,4-linked α-l-fucopyranose, fucose fragments with monotonous 1,3- and 1,4-type linkages (DP up to 3), α-d-Gal-(1→3)-α-L-Fuc disaccharides, and 1,3,4- and 1,2,4-linked fucose branching points. The sulfate groups were found at positions 2 and 4 of fucose and galactose residues. 2SmF2 (up to 800 µg/mL) and 2-DG (up to 8 mM) were not cytotoxic against MDA-MB-231 and SK-MEL-28 as determined by MTS assay. In the soft agar-based model of cancer cell colony formation, fucoidan exhibited weak inhibitory activity at the concentration of 400 µg/mL. However, in combination with low non-cytotoxic concentrations of 2-DG (0.5 or 2 mM), 2SmF2 could effectively inhibit the colony formation of SK-MEL-28 and MDA-MB-231 cells and decreased the number of colonies by more than 50% compared to control at the concentration of 200 µg/mL. Our findings reveal the metabolically oriented effect of fucoidan in combination with a glycolysis inhibitor that may be beneficial for a therapy for aggressive cancers.


Assuntos
Melanoma , Sargassum , Humanos , Fucose , Polissacarídeos/farmacologia
2.
Int J Mol Sci ; 24(15)2023 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-37569428

RESUMO

Melanoma is the most aggressive and treatment-resistant form of skin cancer. It is phenotypically characterized by aerobic glycolysis that provides higher proliferative rates and resistance to cell death. The glycolysis regulation in melanoma cells by means of effective metabolic modifiers represents a promising therapeutic opportunity. This work aimed to assess the metabolically oriented effect and mechanism of action of fucoidan from the brown alga Saccharina cichorioides (ScF) and its carboxymethylated derivative (ScFCM) in combination with 2-deoxy-D-glucose (2-DG) on the proliferation and colony formation of human melanoma cell lines SK-MEL-28, SK-MEL-5, and RPMI-7951. The metabolic profile of melanoma cells was determined by the glucose uptake and Lactate-GloTM assays. The effect of 2-DG, ScF, ScFCM, and their combination on the proliferation, colony formation, and activity of glycolytic enzymes was assessed by the MTS, soft agar, and Western blot methods, respectively. When applied separately, 2-DG (IC50 at 72 h = 8.7 mM), ScF (IC50 at 72 h > 800 µg/mL), and ScFCM (IC50 at 72 h = 573.9 µg/mL) inhibited the proliferation and colony formation of SK-MEL-28 cells to varying degrees. ScF or ScFCM enhanced the inhibiting effect of 2-DG at low, non-toxic concentrations via the downregulation of Glut 1, Hexokinase II, PKM2, LDHA, and pyruvate dehydrogenase activities. The obtained results emphasize the potential of the use of 2-DG in combination with algal fucoidan or its derivative as metabolic modifiers for inhibition of melanoma SK-MEL-28 cell proliferation.


Assuntos
Laminaria , Melanoma , Humanos , Glucose/metabolismo , Laminaria/metabolismo , Melanoma/tratamento farmacológico , Melanoma/metabolismo , Proliferação de Células , Desoxiglucose/farmacologia , Desoxiglucose/uso terapêutico , Linhagem Celular Tumoral
3.
Biomolecules ; 13(3)2023 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-36979354

RESUMO

Cancer is one of the main causes of human mortality worldwide. Despite the advances in the diagnostics, surgery, radiotherapy, and chemotherapy, the search for more effective treatment regimens and drug combinations are relevant. This work aimed to assess the radiomodifying effect and molecular mechanism of action of fucoidan from the brown alga Saccharina cichorioides (ScF) and product of its autohydrolysis (ScF_AH) in combination with pacificusoside D from the starfish Solaster pacificus (SpD) on the model of viability and invasion of three-dimension (3D) human melanoma cells SK-MEL-2. The cytotoxicity of ScF (IC50 JB6 Cl41 > 800 µg/mL; IC50 SK-MEL-2 = 685.7 µg/mL), ScF_AH (IC50 JB6 Cl41/SK-MEL-2 > 800 µg/mL), SpD (IC50 JB6 Cl41 = 22 µM; IC50 SK-MEL-2 = 5.5 µM), and X-ray (ID50 JB6 Cl41 = 11.7 Gy; ID50 SK-MEL-2 = 6.7 Gy) was determined using MTS assay. The efficiency of two-component treatment of 3D SK-MEL-2 cells was revealed for ScF in combination with SpD or X-ray but not for the combination of fucoidan derivative ScF_AH with SpD or X-ray. The pre-treatment of spheroids with ScF, followed by cell irradiation with X-ray and treatment with SpD (three-component treatment) at low non-toxic concentrations, led to significant inhibition of the spheroids' viability and invasion and appeared to be the most effective therapeutic scheme for SK-MEL-2 cells. The molecular mechanism of radiomodifying effect of ScF with SpD was associated with the activation of the initiator and effector caspases, which in turn caused the DNA degradation in SK-MEL-2 cells as determined by the Western blotting and DNA comet assays. Thus, the combination of fucoidan from brown algae and triterpene glycoside from starfish with radiotherapy might contribute to the development of highly effective method for melanoma therapy.


Assuntos
Laminaria , Melanoma , Animais , Humanos , Apoptose , Linhagem Celular Tumoral , Estrelas-do-Mar , Melanoma/metabolismo , DNA/uso terapêutico
4.
Int J Biol Macromol ; 226: 803-812, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36442557

RESUMO

Polysaccharides' derivatives are promising biologically active compounds for biotechnology, nutrition, industries, and are becoming increasingly important in medicine and pharmacy. Laminaran from brown alga Saccharina cichorioides (ScL) was chemically modified to obtain the carboxymethylated derivative (ScLCM) with improved structure and bioactivity. ScLCM was identified as (1 â†’ 3)-ß-D-glucan with -CH2-COOH groups at some positions 2, 4, and 6 of glucose residues. The anticancer activity of ScLCM was studied on the models of viability and invasion of 3D human melanoma SK-MEL-28, breast cancer T-47D, and colorectal carcinoma DLD-1 cells in comparison with native laminaran or its sulfated or aminated derivatives. ScLCM had the highest anticancer and anti-invasive effects among investigated polysaccharides. ScLCM significantly suppressed the viability and invasion of 3D SK-MEL-28 cells via the regulation of the activity of matrix metalloproteinase 9 (MMP 9) and protein kinases of ERK/MAPK signaling pathway. These findings may contribute to the reported anticancer effects of algal polysaccharides' derivatives.


Assuntos
Antineoplásicos , Laminaria , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Glucanos/farmacologia , Glucanos/química , Polissacarídeos/farmacologia , Polissacarídeos/química , Técnicas de Cultura de Células em Três Dimensões
5.
Int J Biol Macromol ; 225: 648-657, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36395953

RESUMO

Six fucoidan fractions were isolated from the brown alga Alaria angusta. Structures of enzymatic hydrolysis products of the fraction 1AaF2 (Fuc:Gal ~ 1:1; 33 % of sulfates) by fucanase from Wenyingzhuangia fucanilytica were studied by chemical and instrumental (NMR spectroscopy and mass-spectrometry) methods. It was shown that 1AaF2 consisted of two structurally different fucoidans: a sulfated 1,3;1,4-α-L-fucan and an enzyme-resistant sulfated and acetylated complex fucogalactan (Fuc:Gal ~ 1:2; 19 % of sulfates) 1AaF2_HMP containing extended 1,3-linked fucose and 1,3/1,4-linked galactose fragments (up to 5 residues). The fractions 1AaF2 and 1AaF2_HMP were a non-cytotoxic, possessed dose-dependent chemopreventive effect on EGF-induced neoplastic cell transformation of mouse normal epidermal JB6 Cl41 cells and inhibited the colony formation of human melanoma SK-MEL-28 cells.


Assuntos
Antineoplásicos , Melanoma , Animais , Camundongos , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Polissacarídeos/farmacologia , Polissacarídeos/química , Sulfatos/química
6.
Int J Mol Sci ; 25(1)2023 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-38203394

RESUMO

Sulfated polysaccharides of brown algae, fucoidans, are known for their anticoagulant properties, similar to animal heparin. Their complex and irregular structure is the main bottleneck in standardization and in defining the relationship between their structure and bioactivity. Fucoidan-active enzymes can be effective tools to overcome these problems. In the present work, we identified the gene fwf5 encoding the fucoidan-active endo-fucanase of the GH168 family in the marine bacterium Wenyingzhuangia fucanilytica CZ1127T. The biochemical characteristics of the recombinant fucanase FWf5 were investigated. Fucanase FWf5 was shown to catalyze the endo-type cleavage of the 1→4-O-glycosidic linkages between 2-O-sulfated α-L-fucose residues in fucoidans composed of the alternating 1→3- and 1→4-linked residues of sulfated α-L-fucose. This is the first report on the endo-1→4-α-L-fucanases (EC 3.2.1.212) of the GH168 family. The endo-fucanase FWf5 was used to selectively produce high- and low-molecular-weight fucoidan derivatives containing either regular alternating 2-O- and 2,4-di-O-sulfation or regular 2-O-sulfation. The polymeric 2,4-di-O-sulfated fucoidan derivative was shown to have significantly greater in vitro anticoagulant properties than 2-O-sulfated derivatives. The results have demonstrated a new type specificity among fucanases of the GH168 family and the prospects of using such enzymes to obtain standard fucoidan preparations with regular sulfation and high anticoagulant properties.


Assuntos
Endometriose , Fucose , Animais , Feminino , Humanos , Catálise , Anticoagulantes/farmacologia , Polissacarídeos , Sulfatos
7.
Int J Biol Macromol ; 206: 614-620, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35219778

RESUMO

The fucoidan SdeF was isolated from brown alga Saccharina dentigera. The structure of the obtained polysaccharide was studied by chemical methods, NMR spectroscopy of the fully and partially desulfated derivatives, and mass spectrometry of the fucoidan fragments, labeled with 18O. The SdeF was shown to be sulfated (40%) 1,3-linked α-L-fucan, with branches at C2. The sulfate groups were found at positions C2 and C4. Derivatives SdeFDS and SdeFPL were obtained by solvolytic desulfation and autohydrolysis of SdeF, respectively. According to 13C NMR data, SdeFDS is 1,3-linked α-L-fucan, while SdeFPL is 4-sulfated 1,3-linked α-L-fucan. Native fucoidan SdeF was shown to be a non-toxic anticancer substance in the model of human malignant melanoma RPMI-7951, colorectal adenocarcinoma HCT-116, and small intestine adenocarcinoma HuTu 80 cells. The partial desulfation of SdeF at C2 and/or the reduction of its Mw, from 229 to 28 kDa, decreased the anticancer activity; complete removal of the sulfated groups and/or Mw reduction to 4.7 kDa further reduced the effect of this polysaccharide.


Assuntos
Adenocarcinoma , Antineoplásicos , Antineoplásicos/química , Antineoplásicos/farmacologia , Humanos , Polissacarídeos/química , Polissacarídeos/farmacologia , Sulfatos
8.
Mar Drugs ; 19(10)2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34677439

RESUMO

Colorectal cancer is one of the most frequent types of malignancy in the world. The search for new approaches of increasing the efficacy of cancer therapy is relevant. This work was aimed to study individual, combined anticancer effects, and molecular mechanism of action of sulfated laminaran AaLs of the brown alga Alaria angusta and protolinckiosides A (PL1), B (PL2), and linckoside L1 (L1) of the starfish Protoreaster lincki using a 3D cell culture model. The 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS), soft agar, 3D spheroids invasion, and Western blotting assays were performed to determine the effect and mechanism of the action of investigated compounds or their combinations on proliferation, colony formation, and the invasion of 3D HCT 116 spheroids. AaLs, PL1, PL2, and L1 individually inhibited viability, colony growth, and the invasion of 3D HCT 116 spheroids in a variable degree with greater activity of linckoside L1. AaLs in combination with L1 exerted synergism of a combined anticancer effect through the inactivation of protein kinase B (AKT) kinase and, consequently, the induction of apoptosis via the regulation of proapoptotic/antiapoptotic proteins balance. The obtained data about the efficacy of the combined anticancer effect of a laminaran derivative of brown algae and polyhydroxysteroid glycosides of starfish open up prospects for the development of new therapeutic approaches for colorectal cancer treatment.


Assuntos
Antineoplásicos/farmacologia , Glucanos/farmacologia , Glicosídeos/farmacologia , Estrelas-do-Mar , Animais , Antineoplásicos/química , Organismos Aquáticos , Proliferação de Células/efeitos dos fármacos , Sinergismo Farmacológico , Quimioterapia Combinada , Glucanos/química , Glicosídeos/química , Células HCT116/efeitos dos fármacos , Humanos
9.
Carbohydr Polym ; 273: 118551, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34560963

RESUMO

Fucoidans are biologically active sulfated polysaccharides of brown algae. They have a great structural diversity and a wide spectrum of biological activity. This review is intended to outline what is currently known about the structures of fucoidans and their radioprotective effect. We classified fucoidans according to their composition and structure, examined the structure of fucoidans of individual representatives of algae, summarized the available data on changes in the yields and compositions of fucoidans during algae development, and focused on information about underexplored radioprotective effect of these polysaccharides. Based on the presented in the review data, it is possible to select algae, which are the sources of fucoidans of desired structures and to determine the best time to harvest them. The use of high purified polysaccharides with established structures increase the value of studies of their biological effects and the determination of the dependence "structure - biological effect".


Assuntos
Polissacarídeos/química , Polissacarídeos/farmacologia , Protetores contra Radiação/farmacologia , Animais , Apoptose/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Galactose/análise , Humanos , Estrutura Molecular , Protetores contra Radiação/química , Sulfatos/química
10.
Int J Biol Macromol ; 185: 31-39, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34144063

RESUMO

This study was aimed to determine the efficacy of combination of fucoidan from the brown algae Fucus evanescens (FeF) or its derivatives with thornasteroside A (ThA) or asteropsiside A (AsA) from the starfish Asteropsis carinifera in combating human melanoma cells. In vitro MTS and soft agar methods were performed to determine effect of FeF, its derivatives, ThA, AsA or their combination on proliferation and colony formation of SK-MEL-28 cells in 2D and 3D culture. Desulfation of FeF, but not deacetylation, led decreasing of its Mw and anti-proliferative activity. The combinatorial effect of FeF with ThA and AsA depended on the sequences of treatment by compounds. There was additive anticancer effect of FeF with ThA or AsA during simultaneous treatment of cells. ThA and AsA were not active against SK-MEL-28 cells after their pre-treatment with FeF. Potential synergism of action was identified only when SK-MEL-28 cells were pre-treated with ThA and AsA and then by FeF. This process going through the regulation of MEK1/2/ERK1/2/MSK1 pathway and expression of the cell cycle proteins as determined by Western Blot. Thus, the combination of fucoidan with the asterosaponins opens up the prospects for the development of effective combined chemotherapeutic methods for melanoma treatment.


Assuntos
Antineoplásicos/farmacologia , Fucus/química , Melanoma/metabolismo , Polissacarídeos/farmacologia , Saponinas/farmacologia , Estrelas-do-Mar/química , Animais , Antineoplásicos/química , Carbazóis/química , Carbazóis/farmacologia , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sinergismo Farmacológico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Melanoma/tratamento farmacológico , Modelos Biológicos , Polissacarídeos/química , Saponinas/química
11.
Int J Biol Macromol ; 183: 1427-1435, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34023368

RESUMO

The aim of this study was to establish the fine structure of fucoidan from Sargassum oligocystum and to study the radiosensitizing effect of fucoidans from three algae of genus Sargassum (S. oligocystum, S. duplicatum, and S. feldmannii) with different structures. The fucoidan SoF2 from S. oligocystum was sulfated (32%) galactofucan (Fuc:Gal = 2:1), with a Mw of 183 kDa (Mw/Mn = 2.0). Its supposed structure was found to be predominantly 1,3-linked fucose as the main chain, with branching points at C2 and C4. The branches could be single galactose and/or fucose short chains with terminal galactose residues. Sulfate groups were found at positions C3, C2, and/or C4 of fucose residues and at C2 and/or C4 of galactose residues. The radiosensitizing effect of galactofucans from S. oligocystum, S. duplicatum, and S. feldmannii against human melanoma SK-MEL-28, colon HT-29, and breast MDA-MB-231 cancer cells was investigated. The influence of all investigated polysaccharides treatments with/without X-ray radiation on colony formation of human melanoma cells SK-MEL-28 was weak. Fucoidan from S. feldmannii has been shown to be the most promising radiosensitizing compound against human colon HT-29 and breast MDA-MB-231 cancer cells.


Assuntos
Polissacarídeos/química , Sargassum/química , Linhagem Celular Tumoral , Células HT29 , Humanos , Radiossensibilizantes/química
12.
Carbohydr Polym ; 250: 116921, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33049835

RESUMO

Polysaccharide fractions of alginate, laminarans and fucoidans were obtained from the brown alga Tauya basicrassa. Yields of alginate and laminarans were large (19.7 % and 5.62 %, respectively), whereas the content of fucoidans (0.52 %) was not significant. Alginate and laminarans had typical structures for those substances. Fucoidans were low- and medium-sulfated heterogeneous polysaccharides. The fucoidan fraction 1TbF1 was sulfated fucogalactan containing a backbone from 1,6-linked residues of ß-d-galactopyranose with branches at C3 and C4, terminal fucose and galactose residues and fragments from 1,3-; 1,4-; and 1,2-fucose residues. Sulfate groups were found at positions 2 and 4 of fucose, and positions 2, 3 and 4 of galactose residues. Laminaran 2TbL was subjected to a sulfation to obtain the derivative 2TbLS with partial sulfation (46 %) at C2, C4 and C6. It was shown that 2TbL and 2TbLS inhibited colony formation of sensitize-tested colon cancer cells HT-29 and HCT-116 to X-ray radiation.


Assuntos
Neoplasias do Colo/tratamento farmacológico , Glucanos/farmacologia , Polissacarídeos/química , Radiossensibilizantes/farmacologia , Sulfatos/química , Antineoplásicos , Neoplasias do Colo/patologia , Glucanos/química , Humanos , Polissacarídeos/farmacologia , Radiossensibilizantes/química , Células Tumorais Cultivadas , Raios X
13.
Carbohydr Polym ; 250: 117007, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33049875

RESUMO

Laminarans are currently the focus of attention in regard to the selection of prospective agents for the prevention and treatment of cancer. Laminaran from Saccharina cichorioides was aminated to heighten anticancer and radiosensitizing activities and elucidate its molecular mode of action. Aminated laminaran, ScLNH2, was identified as 1,3-ß-d-glucan with -CH2-CH(OH)-CH2-NH2 group at the C6 of branches. ScLNH2 selectively inhibited the viability and colony formation in the MDA-MB-231 cell line of triple negative breast cancer cells. ScLNH2 possessed synergism with radiation, resulting in a decreased number of colonies of MDA-MB-231 cells. The mechanism underling the radiosensitizing effect of ScLNH2 was associated with apoptosis induction via regulation of caspases 9 and 3 and PARP enzyme, preventing the repair of DNA damage in irradiated cells. These findings confirmed that combination therapy by aminated laminaran and radiation might play a role in the optimization of therapy for an aggressive form of human breast cancer.


Assuntos
Aminas/química , Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Glucanos/farmacologia , Radiossensibilizantes/farmacologia , Apoptose , Neoplasias da Mama/patologia , Proliferação de Células , Feminino , Glucanos/química , Humanos , Técnicas In Vitro , Células Tumorais Cultivadas
14.
Int J Biol Macromol ; 163: 1010-1025, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32663561

RESUMO

The laminarans are biologically active water-soluble polysaccharide (1,3;1,6-ß-D-glucans) of brown algae. These polysaccharides are an attractive object for research due to its relatively simple structure, low toxicity, and various biological effects. 1,3-ß-D-glucanases are an effective tool for studying the structure of laminarans, and can also be used to obtain new biologically active derivatives. This review is to outline what is currently known about laminarans and enzymes that catalyze of their transformation. We focused on information about sources, structure and properties of laminarans and 1,3-ß-D-glucanases, methods of obtaining and structural elucidation of laminarans, and biological activity of laminarans and products of their enzymatic transformation. It has an increased focus on the immunomodulating and anticancer activity of laminarans and their derivatives.


Assuntos
Glucana 1,3-beta-Glucosidase/química , Glucanos/química , Animais , Humanos , Polissacarídeos/química , Relação Estrutura-Atividade
15.
Carbohydr Polym ; 221: 157-165, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31227154

RESUMO

The sulfated α-l-fucans ScF and LlF were obtained from brown algae of the Laminariaceae family (Saccharina cichorioides and Laminaria longipes). According to spectroscopy NMR, the LlF fucan predominantly contained the →3)-α-l-Fucp-(2SO3-)-(1→4)-α-l-Fucp-(1→2)-α-l-Fucp-(4SO3-)-(1→ repeating units, with small amounts of disaccharide 1,4-linked fragments and 3-sulfated fucose residues. Mass spectrometric analysis revealed the presence of the following fragments in the fucan structure: α-l-Fucp-(2SO3-)-(1→4)-α-l-Fucp-(2SO3-)-(1→3)-α-l-Fucp-(4SO3-); α-l-Fucp-(2,4SO3-)-(1→3)-α-l-Fucp-(1→3)-α-l-Fucp-(4SO3-); α-l-Fucp-(2SO3-)-(1→2)-α-l-Fucp; α-l-Fucp-(2SO3-)-(1→2)-α-l-Fucp-(4SO3-); α-l-Fucp-(2SO3-)-(1→3)-α-l-Fucp; α-l-Fucp-(2,4SO3-)-(1→3)-α-l-Fucp; α-l-Fucp-(4SO3-)-(1→4)-α-l-Fucp; and α-l-Fucp-(4SO3-)-(1→4)-α-l-Fucp-(2SO3-). Both ScF and LlF fucoidans inhibited colony formation and growth of melanoma and colon cancer cells and sensitize-tested cancer cells to X-ray radiation to a comparable degree.


Assuntos
Antineoplásicos/farmacologia , Laminaria/química , Polissacarídeos/farmacologia , Radiossensibilizantes/farmacologia , Antineoplásicos/química , Sequência de Carboidratos , Linhagem Celular Tumoral , Humanos , Polissacarídeos/química , Radiossensibilizantes/química
16.
Carbohydr Polym ; 206: 539-547, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30553355

RESUMO

The laminarans are neutral water-soluble ß-D-glucans of brown algae possessing potent immunomodulating, radioprotective, and anticancer activities. The aim of the present study was to investigate in vitro anticancer, radioprotective, and radiosensitizing activities of laminaran from brown alga Dictyota dichotoma and its sulfated derivative. The native and sulfated laminarans by themselves at non-toxic doses possessed significant anticancer activity against melanoma cells. Both polysaccharides protected normal epidermal cells, while only sulfated laminaran was able to sensitize melanoma cells to X-rays irradiation resulting in significant inhibition of cell proliferation, colony formation, and migration of cancer cells. The molecular mechanism of this action was related to the inhibition of MMP-2 and MMP-9 proteinases activity as well as down-regulation of kinases' phosphorylation of ERK1/2 signaling cascade. Taken together, the combination of sulfated derivative of laminaran from D. dichotoma with X-ray may serve as a potential treatment strategy for human melanoma.


Assuntos
Antineoplásicos/farmacologia , Glucanos/farmacologia , Polissacarídeos/farmacologia , Protetores contra Radiação/farmacologia , Radiossensibilizantes/farmacologia , Animais , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Humanos , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Inibidores de Metaloproteinases de Matriz/farmacologia , Camundongos , Proteína Quinase 1 Ativada por Mitógeno , Proteína Quinase 3 Ativada por Mitógeno/metabolismo
17.
Int J Biol Macromol ; 124: 220-228, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30496854

RESUMO

Fucoidans are valuable biologically active polysaccharides of brown algae. The aim of this study was to investigate the structure of fucoidan from Sargassum feldmannii and the anticancer effects of native and modified polysaccharides from S. feldmannii and S. duplicatum. The structure of sulfated (25.3%) galactofucan SfF2 (Fuc/Gal = 72/28 mol%) from S. feldmannii was investigated by NMR spectroscopy of desulfated derivative and mass spectrometry of fucoidan fragments labelled with 18O. SfF2 was shown to contain the main chain from 1,3-linked α-l-fucopyranose and ß-d-galactopyranose residues with fucose branches at C4 and C6 of galactose residues and C2 of fucose residues. The following fragments were also identified in SfF2: Fuc-(1,4)-Fuc, Gal-(1,3)-Gal, and Gal-(1,4)-Gal. The sulfate groups occupied positions C2, C3, and C4 of fucose residues and C2, C3, C4, and C6 of galactose residues. The galactofucans from S. feldmannii, S. duplicatum, and their derivatives exhibited no cytotoxicity in vitro. The native and deacetylated fucoidans (200 µg/mL) inhibited colony formation of human colon cancer cells (DLD-1, HT-29, and HCT-116). Both desulfated fucoidans possessed weak anticancer activity.


Assuntos
Antineoplásicos/química , Polissacarídeos/química , Sargassum/química , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Neoplasias do Colo/tratamento farmacológico , Galactose/química , Células HT29 , Humanos , Polissacarídeos/isolamento & purificação , Polissacarídeos/farmacologia , Sulfatos/química
18.
Int J Biol Macromol ; 117: 1101-1109, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-29885396

RESUMO

In the present study, three sulfated polysaccharides, two fractions of fucosylated chondroitin sulfates, and one sulfated fucan were isolated from the body wall of the Vietnamese sea cucumber Stichopus variegatus. The structure of the sulfated fucan fraction SvF3 from S. variegatus was investigated for the first time. According to NMR spectroscopy data, the sulfated fucan SvF3 contained 1,2- and 1,3-linked α-l-fucopyranose residues. Sulfate groups were found at the 2 and/or 4 positions. The structural analysis of fucoidan was assisted by tandem mass spectrometry; the recently-developed technique of autohydrolysis in heavy­oxygen water for the obtaining of selectively labeled fucoidan fragments was applied. The labeling (+2 Da mass shift at the reducing end) allowed us to assign MS/MS data unambiguously, and thus to confirm the NMR data and revealed minor sulfation at position 3. It was shown that the sulfated fucan SvF3 was not cytotoxic to human breast cancer T-47D and MDA-MB-231 cell lines, and it inhibited colony formation of those cells in vitro. SvF3 also possessed slight activity against migration of MDA-MB-231 cells in vitro.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Polissacarídeos/química , Polissacarídeos/farmacologia , Animais , Antineoplásicos/isolamento & purificação , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Hidrólise , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Peso Molecular , Polissacarídeos/isolamento & purificação , Pepinos-do-Mar/química , Relação Estrutura-Atividade , Temperatura
19.
Carbohydr Polym ; 184: 260-268, 2018 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-29352918

RESUMO

The sulfated and acetylated fucoidan fraction, containing fucose, galactose, mannose, glucose and uronic acid residues, was isolated from the brown alga Padina boryana. The structure of galactofucan part was studied after different modifications by NMR spectroscopy and mass spectrometry. It was shown that galactofucan contained the main chain of alternating 1,4-linked α-l-fucopyranose and 1,3-linked ß-d-Galactopyranose. Single fucose residues were found as branches at C4 of galactose residues. Also, fucoidan contained 1,3- or 1,4-linked Fuc-Fuc and Gal-Gal fragments. The sulfate groups occupied positions C2, C3 and C4 of both fucose and galactose residues, which was shown by tandem mass spectrometry of fragments, labeled with heavy-oxygen. The anticancer effect of native and modified fucoidan fractions was studied in vitro on the colorectal carcinoma cells DLD-1 and HCT-116. All fucoidans had no cytotoxicity under 400 µg/mL and inhibited colony formation of cancer cells at concentration of 200 µg/mL.


Assuntos
Polissacarídeos/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Glucanos/química , Humanos , Camundongos , Polissacarídeos/farmacologia , Sargassum/química
20.
Carbohydr Polym ; 180: 21-28, 2018 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-29103498

RESUMO

The laminaran DdL and fucoidan DdF were obtained from the brown alga Dictyota dichotoma. DdF was a sulfated (28.9%) and acetylated heteropolysaccharide containing fucose, galactose, mannose and glucose (57.9, 20.4, 12.4 and 9.2mol%, respectively). DdL was a 1,3;1,6-ß-d-glucan with the main chain built from 1,3-linked glucose residues and single glucose residue in branches at C6 (one branch on three glucose residues of the main chain). Sulfated (43.7%) laminaran DdLs was obtained from DdL by sulfation. It was determined that sulfates occur at C2, C4 and C6 of glucose residues. The anticancer effect of DdF, DdL, and DdLs (200µg/mL) was studied in vitro on colon cancer cells HCT-116, HT-29, and DLD-1. The effect of polysaccharides (40µg/mL) on colony formation of DLD-1 cancer cells after irradiation (4Gy) was investigated first. All polysaccharides showed a synergistic effect with X-ray irradiation against cancer cells, decreasing the amount and size of cancer cells colonies.


Assuntos
Antineoplásicos/química , Glucanos/química , Polissacarídeos/química , Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Glucanos/farmacologia , Células HCT116 , Células HT29 , Humanos , Polissacarídeos/farmacologia
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