RESUMO
Three new monosulfated polyhydroxysteroid glycosides, spiculiferosides A (1), B (2), and C (3), along with new related unsulfated monoglycoside, spiculiferoside D (4), were isolated from an ethanolic extract of the starfish Henricia leviuscula spiculifera collected in the Sea of Okhotsk. Compounds 1-3 contain two carbohydrate moieties, one of which is attached to C-3 of the steroid tetracyclic core, whereas another is located at C-24 of the side chain of aglycon. Two glycosides (2, 3) are biosides, and one glycoside (1), unlike them, includes three monosaccharide residues. Such type triosides are a rare group of polar steroids of sea stars. In addition, the 5-substituted 3-OSO3-α-L-Araf unit was found in steroid glycosides from starfish for the first time. Cell viability analysis showed that 1-3 (at concentrations up to 100 µM) had negligible cytotoxicity against human embryonic kidney HEK293, melanoma SK-MEL-28, breast cancer MDA-MB-231, and colorectal carcinoma HCT 116 cells. These compounds significantly inhibited proliferation and colony formation in HCT 116 cells at non-toxic concentrations, with compound 3 having the greatest effect. Compound 3 exerted anti-proliferative effects on HCT 116 cells through the induction of dose-dependent cell cycle arrest at the G2/M phase, regulation of expression of cell cycle proteins CDK2, CDK4, cyclin D1, p21, and inhibition of phosphorylation of protein kinases c-Raf, MEK1/2, ERK1/2 of the MAPK/ERK1/2 pathway.
Assuntos
Antineoplásicos , Glicosídeos , Estrelas-do-Mar , Animais , Humanos , Estrelas-do-Mar/química , Glicosídeos/farmacologia , Glicosídeos/química , Glicosídeos/isolamento & purificação , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Esteroides/farmacologia , Esteroides/química , Esteroides/isolamento & purificação , Proliferação de Células/efeitos dos fármacosRESUMO
Two new steroid 3ß,21-disulfates (1, 2) and two new steroid 3ß,22- and 3α,22-disulfates (3, 4), along with the previously known monoamine alkaloid tryptamine (5) were found in the ethanolic extract of the Far Eastern slime sea star Pteraster marsippus. Their structures were determined on the basis of detailed analysis of one-dimensional and two-dimensional NMR, HRESIMS, and HRESIMS/MS data. Compounds 1 and 2 have a Δ22-21-sulfoxy-24-norcholestane side chain. Compounds 3 and 4 contain a Δ24(28)-22-sulfoxy-24-methylcholestane side chain, which was first discovered in the polar steroids of starfish and brittle stars. The influence of substances 1-4 on cell viability, colony formation, and growth of human breast cancer T-47D, MCF-7, and MDA-MB-231 cells was investigated. It was shown that compounds 1 and 2 possess significant colony-inhibiting activity against T-47D cells, while compounds 3 and 4 were more effective against MDA-MB-231 cells.
Assuntos
Neoplasias da Mama , Estrelas-do-Mar , Humanos , Animais , Feminino , Neoplasias da Mama/tratamento farmacológico , Equinodermos , Esteroides/farmacologia , AminasRESUMO
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 terapêuticoRESUMO
Six previously unknown triterpene glycosides, pacificusosides L-Q (1-6), and two previously known triterpene glycosides, cucumariosides B1 (7) and A5 (8), were isolated from an alcoholic extract of Pacific sun star, Solaster pacificus. The structures of 1-6 were determined using 1D and 2D NMR, ESIMS, and chemical modifications. Compound 1 is a rare type of triterpene glycoside with non-holostane aglycon, having a linear trisaccharide carbohydrate chain. Pacificusosides M-P (2-5) have new structures containing a Δ8(9)-3,16,18-trihydroxy tetracyclic triterpene moiety. This tetracyclic fragment in sea star or sea cucumber triterpene glycosides was described for the first time. All the compounds under study exhibit low or moderate cytotoxic activity against colorectal carcinoma HCT 116 cells, and breast cancer MDA-MB-231 cells were assessed by MTS assay. Compound 2 effectively suppresses the colony formation of cancer cells at a non-toxic concentration, using the soft-agar assay. A scratch assay has shown a significant anti-invasive potential of compound 2 against HCT 116 cells, but not against MDA-MB-231 cells.
Assuntos
Neoplasias Colorretais , Glicosídeos , Humanos , Glicosídeos/farmacologia , Bioensaio , Células HCT116 , Projetos de PesquisaRESUMO
Three new ceramides (1−3) and three new cerebrosides (4, 8, and 9), along with three previously known cerebrosides (ophidiocerebrosides C (5), D (6), and CE-3-2 (7)), were isolated from a deep-sea starfish species, the orange cookie starfish Ceramaster patagonicus. The structures of 1−4, 8, and 9 were determined by the NMR and ESIMS techniques and also through chemical transformations. Ceramides 1−3 contain iso-C21 or C23 Δ9-phytosphingosine as a long-chain base and have C16 or C17 (2R)-2-hydroxy-fatty acids of the normal type. Cerebroside 4 contains C22 Δ9-sphingosine anteiso-type as a long-chain base and (2R)-2-hydroxyheptadecanoic acid of the normal type, while compounds 8 and 9 contain saturated C-17 phytosphingosine anteiso-type as a long-chain base and differ from each other in the length of the polymethylene chain of (2R)-2-hydroxy-fatty acids of the normal type: C23 in 8 and C24 in 9. All the new cerebrosides (4, 8, and 9) have ß-D-glucopyranose as a monosaccharide residue. The composition of neutral sphingolipids from C. patagonicus was described for the first time. The investigated compounds 1−3, 5−7, and 9 exhibit slight to moderate cytotoxic activity against human cancer cells (HT-29, SK-MEL-28, and MDA-MB-231) and normal embryonic kidney cells HEK293. Compounds 2, 5, and 6 at a concentration of 20 µM inhibit colony formation of MDA-MB-231 cells by 68%, 54%, and 68%, respectively. The colony-inhibiting activity of compounds 2, 5, and 6 is comparable to the effect of doxorubicin, which reduces the number of colonies by 70% at the same concentration.
Assuntos
Ceramidas , Cerebrosídeos , Animais , Humanos , Cerebrosídeos/farmacologia , Cerebrosídeos/química , Ceramidas/farmacologia , Esfingosina , Estrelas-do-Mar , Células HEK293 , Esfingolipídeos , Ácidos Graxos , Monossacarídeos , DoxorrubicinaRESUMO
New steroidal 3ß,21-disulfates (2-4), steroidal 3ß,22-disulfate (5), and the previously known related steroidal 3ß,21-disulfate (1) were isolated from the ethanolic extract of the Far Eastern starfish Pteraster marsippus, collected off Urup Island in the Sea of Okhotsk. The structures of these compounds were determined by intensive NMR and HRESIMS techniques as well as by chemical transformations. Steroids 2 and 3 have an oxo-group in the tetracyclic nucleus at position C-7 and differ from each other by the presence of the 5(6)-double bond. The Δ24-22-sulfoxycholestane side chain of the steroid 5 has not been found previously in the starfish or ophiuroid steroids. The cytotoxic activities of 1, 4, 5, and the mixture of 2 and 3 were determined on the models of 2D and 3D cultures of human epithelial kidney cells (HEK293), melanoma cells (SK-MEL-28), small intestine carcinoma cells (HuTu80), and breast carcinoma cells (ZR-75-1). The mixture of 2 and 3 revealed a significant inhibitory effect on the cell viability of human breast carcinoma ZR-75-1 cells, but other tested compounds were less effective.
Assuntos
Antineoplásicos , Estrelas-do-Mar/química , Esteroides , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Técnicas de Cultura de Células , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Misturas Complexas/química , Sinergismo Farmacológico , Humanos , Esteroides/química , Esteroides/isolamento & purificação , Esteroides/farmacologiaRESUMO
Sea stars or starfish (class Asteroidea) and holothurians or sea cucumbers (class Holothuroidea), belonging to the phylum Echinodermata (echinoderms), are characterized by different sets of glycosidic metabolites: the steroid type in starfish and the triterpene type in holothurians. However, herein we report the isolation of eight new triterpene glycosides, pacificusosides D−K (1−3, 5−9) along with the known cucumarioside D (4), from the alcoholic extract of the Far Eastern starfish Solaster pacificus. The isolated new compounds are closely related to the metabolites of sea cucumbers, and their structures of 1−3 and 5−9 were determined by extensive NMR and ESIMS techniques. Compounds 2, 5, and 8 have a new type of tetrasaccharide chain with a terminal non-methylated monosaccharide unit. Compounds 3, 6, and 9 contain another new type of tetrasaccharide chain, having 6-O-SO3-Glc as one of the sugar units. The cytotoxic activity of 1−9 against non-cancerous mouse epidermal cells JB6 Cl41 and human melanoma cell lines SK-MEL-2, SK-MEL-28, and RPMI-7951 was determined by MTS assay. Compounds 1, 3, 4, 6, and 9 showed potent cytotoxicity against these cell lines, but the cancer selectivity (SI > 9) was observed only against the SK-MEL-2 cell line. Compounds 1, 3, 4, 6, and 9 at the non-toxic concentration of 0.1 µM significantly inhibited neoplastic cell transformation of JB6 Cl41 cells induced by chemical carcinogens (EGF, TPA) or ionizing radiation (X-rays and UVB). Moreover, compounds 1 and 4 at the non-toxic concentration of 0.1 µM possessed the highest inhibiting activity on colony formation among the investigated compounds and decreased the colonies number of SK-MEL-2 cells by 64% and 70%, respectively. Thus, triterpene glycosides 1 and 4 can be considered as prospective cancer-preventive and anticancer-compound leaders.
Assuntos
Anticarcinógenos/farmacologia , Antineoplásicos/farmacologia , Glicosídeos/farmacologia , Estrelas-do-Mar/química , Triterpenos/farmacologia , Animais , Anticarcinógenos/isolamento & purificação , Antineoplásicos/isolamento & purificação , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Transformação Celular Neoplásica/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Glicosídeos/isolamento & purificação , Hemólise/efeitos dos fármacos , Humanos , Camundongos , Triterpenos/isolamento & purificaçãoRESUMO
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 , Phaeophyceae , 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 , HumanosRESUMO
Sphingolipids are complex lipids widespread in nature as structural components of biomembranes. Commonly, the sphingolipids of marine organisms differ from those of terrestrial animals and plants. The gangliosides are the most complex sphingolipids characteristic of vertebrates that have been found in only the Echinodermata (echinoderms) phylum of invertebrates. Sphingolipids of the representatives of the Asteroidea and Holothuroidea classes are the most studied among all echinoderms. In this review, we have summarized the data on sphingolipids of these two classes of marine invertebrates over the past two decades. Recently established structures, properties, and peculiarities of biogenesis of ceramides, cerebrosides, and gangliosides from starfishes and holothurians are discussed. The purpose of this review is to provide the most complete information on the chemical structures, structural features, and biological activities of sphingolipids of the Asteroidea and Holothuroidea classes.
Assuntos
Pepinos-do-Mar/química , Esfingolipídeos/química , Estrelas-do-Mar/química , Animais , Organismos Aquáticos/química , Ceramidas/biossíntese , Ceramidas/química , Cerebrosídeos/química , Equinodermos , Gangliosídeos/química , Estrutura MolecularRESUMO
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/químicaRESUMO
Three new triterpene glycosides, pacificusosides A-C (1-3), and three previously known triterpene glycosides, cucumariosides C1 (4), C2 (5), and A10 (6), were isolated from the alcoholic extract of the Far Eastern starfish Solaster pacificus. The structures of 1-3 were elucidated by extensive NMR and ESIMS techniques and chemical transformations. Compound 1 has a novel, unique structure, containing an aldehyde group of side chains in its triterpene aglycon. This structural fragment has not previously been found in the sea cucumber triterpene glycosides or starfish steroidal glycosides. Probably, pacificusoside A (1) is a product of the metabolism of the glycoside obtained through dietary means from a sea cucumber in the starfish. Another two new triterpene glycosides (2, 3) have closely related characteristics to sea cucumber glycosides. The cytotoxicity of compounds 1-6 was tested against human embryonic kidney HEK 293 cells, colorectal carcinoma HT-29 cells, melanoma RPMI-7951 cells, and breast cancer MDA-MB-231 cells using MTS assay. Compounds 4-6 revealed the highest cytotoxic activity against the tested cell lines, while the other investigated compounds had moderate or slight cytotoxicity. The cytotoxic effects of 2-6 were reduced by cholesterol like the similar effects of the previously investigated individual triterpene glycosides. Compounds 3, 4, and 5 almost completely suppressed the colony formation of the HT-29, RPMI-7951, and MDA-MB-231 cells at a nontoxic concentration of 0.5 µM.
Assuntos
Glicosídeos/farmacologia , Estrelas-do-Mar/química , Triterpenos/farmacologia , Animais , Antineoplásicos/farmacologia , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Linhagem Celular Tumoral , Glicosídeos/química , Glicosídeos/isolamento & purificação , Células HEK293 , Humanos , Conformação Molecular , Espectroscopia de Prótons por Ressonância Magnética , Triterpenos/química , Triterpenos/isolamento & purificação , Ensaio Tumoral de Célula-TroncoRESUMO
New asterosaponin, acanthaglycoside G (1), along with three previously known steroidal oligoglycosides (2â4), were isolated from the ethanolic extract of the starfish Acanthaster planci, collected off the coast of Vietnam. The structure of 1 was mainly elucidated by extensive NMR and ESIMS techniques as sodium 6-O-{ß-D-fucopyranosyl-(1â2)-ß-D-quinovopyranosyl-(1â4)-[ß-D-quinovopyranosyl-(1â2)]-ß-D-quinovopyranosyl-(1â3)-ß-D-quinovopyranosyl}-6α-hydroxy-5α-pregn-9(11)-en-20-one-3ß-yl sulfate. Compounds 3 and 4 showed slight cytotoxic activities against cancer RPMI-7951, HT-29, and MDA-MB-231 cell lines, but effectively inhibited in non-toxic concentrations colony formation of HT-29 and MDA-MB-231 cells and cell migration of MDA-MB-231 cells. Compounds 1 and 2 were inactive or less active, respectively.
Assuntos
Saponinas/isolamento & purificação , Saponinas/farmacologia , Estrelas-do-Mar/química , Clima Tropical , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Humanos , Espectroscopia de Prótons por Ressonância Magnética , Saponinas/química , VietnãRESUMO
Two new natural compounds, sulfated polyhydroxysteroid, microdiscusol G (1), and polyhydroxysteroid bioside, microdiscusoside A (2), along with eight previously known polar steroid substances 3-10, were isolated from the Arctic starfish Asterias microdiscus. The structures of 1 and 2 have been elucidated by extensive 1D and 2D NMR spectroscopy and HRESIMS techniques. The 28-sulfooxy-24-methylcholestane side chain in 1 has been found among starfish steroid metabolites for the first time. Steroid saponins 9 and 10 exhibited cytotoxic effects against normal cells JB6 Cl41 and cancer cells HT-29, MDA-MB-231, THP-1, and Raji and effectively suppressed cell proliferation and colony formation of cancer cells HT-29 and MDA-MB-231 in non-toxic concentrations. Compounds 5, 7, and 8 were inactive or less active in the same experiments.
Assuntos
Antineoplásicos , Asterias , Saponinas , Animais , Humanos , Saponinas/farmacologia , Estrelas-do-Mar , Esteroides/farmacologiaRESUMO
Asterosaponins are a class of steroid oligoglycosides isolated from starfish with characteristic structures and diverse biological activities. In this review, we have attempted to combine the most important data concerning asterosaponins and give a list of these secondary metabolites with their structural peculiarities. The purpose of this review is to provide a brief but as complete as possible principal information about their chemical structures, taxonomic distribution in the marine environment, distribution in different geographical areas and depths, some properties, biological activities, and functions. Some other rare steroid metabolites from starfish, closely related in structures and probably biogenesis to asterosaponins, are also discussed.
Assuntos
Oligossacarídeos/farmacologia , Saponinas/farmacologia , Animais , Humanos , Estrutura Molecular , Oligossacarídeos/química , Saponinas/química , Relação Estrutura-AtividadeRESUMO
Four new conjugates, esters of polyhydroxysteroids with long-chain fatty acids (1-4), were isolated from the deep-water Far Eastern starfish Ceramaster patagonicus. The structures of 1-4 were established by NMR and ESIMS techniques as well as chemical transformations. Unusual compounds 1-4 contain the same 5α-cholestane-3ß,6ß,15α,16ß,26-pentahydroxysteroidal moiety and differ from each other in the fatty acid units: 5'Z,11'Z-octadecadienoic (1), 11'Z-octadecenoic (2), 5'Z,11'Z-eicosadienoic (3), and 7'Z-eicosenoic (4) acids. Previously, only one such steroid conjugate with a fatty acid was known from starfish. After 72 h of cell incubation, using MTS assay it was found that the concentrations of compounds 1, 2, and 3 that caused 50% inhibition of growth (IC50) of JB6 Cl41 cells were 81, 40, and 79 µM, respectively; for MDA-MB-231 cells, IC50 of compounds 1, 2, and 3 were 74, 33, and 73 µM, respectively; for HCT 116 cells, IC50 of compounds 1, 2, and 3 were 73, 31, and 71 µM, respectively. Compound 4 was non-toxic against tested cell lines even in three days of treatment. Compound 2 (20 µM) suppressed colony formation and migration of MDA-MB-231 and HCT 116 cells.
Assuntos
Antineoplásicos/farmacologia , Linhagem Celular Tumoral/efeitos dos fármacos , Ácidos Graxos/farmacologia , Estrelas-do-Mar , Esteroides/farmacologia , Animais , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Ácidos Graxos/química , Oceanos e Mares , Federação Russa , Esteroides/química , Relação Estrutura-AtividadeRESUMO
Four new polyhydroxylated steroids 1-4 were isolated along with two previously known related steroids 5 and 6 from the methanolic extract of the starfish Anthenoides laevigatus collected off the coastal waters of Vietnam. Structures of new compounds were substantially elucidated by one-dimensional (1D) and two-dimensional (2D) NMR spectroscopy and HRESIMS techniques. Heptaol 1 and hexaol 2 contain the common 5α-cholestane skeleton, while hexaol 3 and heptaol 4 have the rare among starfish steroid compounds 5ß-cholestane skeleton. Compounds 1, 5, and 6 do not show cytotoxic effects against normal JB6 Cl41 and cancer HT-29 and MDA-MB-231 cells, however they inhibit cell proliferation and colony formation of cancer HT-29 and MDA-MB-231 cells.
Assuntos
Antineoplásicos , Proliferação de Células/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Estrelas-do-Mar/química , Esteroides , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Células HT29 , Humanos , Estrutura Molecular , Neoplasias/metabolismo , Neoplasias/patologia , Ressonância Magnética Nuclear Biomolecular , Esteroides/química , Esteroides/isolamento & purificação , Esteroides/farmacologia , VietnãRESUMO
From the MeOH extract of the Vietnamese sea cucumber Holothuria edulis, eight triterpene glycosides (1-8), including one new compound namely holothurin A5 (1), were isolated by using various chromatographic separations. Their structures were established by spectroscopic experiments including 1D, 2D NMR and HR-ESI-MS. Holothurin A5 (1) has a hydroperoxy group at C-25. To the best of our knowledge, this is the first report of this group in triterpene saponins obtained from sea cucumbers to date. In addition, the in vitro cytotoxicity against five human cancer cell lines (HepG2, KB, LNCaP, MCF7 and SK-Mel2) of all isolated compounds was also evaluated using SRB assays.
Assuntos
Glicosídeos/isolamento & purificação , Holothuria/química , Pepinos-do-Mar/química , Triterpenos/isolamento & purificação , Animais , Linhagem Celular Tumoral , Citotoxinas/química , Citotoxinas/isolamento & purificação , Citotoxinas/farmacologia , Glicosídeos/química , Humanos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Saponinas/química , Saponinas/isolamento & purificação , Triterpenos/química , VietnãRESUMO
Glycoconjugated and other polar steroids of starfish have unique chemical structures and show a broad spectrum of biological activities. However, their biological functions remain not well established. Possible biological roles of these metabolites might be indicated by the studies on their distribution in the organism-producer. In order to investigate the localization of polar steroids in body components of the Far Eastern starfish Lethasterias fusca, chemical constituents of body walls, gonads, stomach, pyloric caeca, and coelomic fluid were studied by nanoflow liquid chromatography/mass spectrometry with captive spray ionization (nLC/CSI-QTOF-MS). It has been shown that the levels of polar steroids in the studied body components are qualitatively and quantitatively different. Generally, the obtained data confirmed earlier made assumptions about the digestive function of polyhydroxysteroids and protective role of asterosaponins. The highest level of polar steroids was found in the stomach. Asterosaponins were found in all body components, the main portion of free polyhydroxysteroids and related glycosides were located in the pyloric caeca. In addition, a great inter-individual variability was found in the content of most polar steroids, which may be associated with the peculiarities in their individual physiologic status.
Assuntos
Glicosídeos/metabolismo , Hidroxiesteroides/metabolismo , Saponinas/metabolismo , Estrelas-do-Mar/metabolismo , Animais , Cromatografia Líquida/métodos , Esteroides/metabolismo , Estômago/fisiologia , Espectrometria de Massas em Tandem/métodosRESUMO
Despite significant advances in the understanding, prevention, and treatment of cancer, the disease continues to affect millions of people worldwide. Chemoradiation therapy is a rational approach that has already proven beneficial for several malignancies. However, the existence of toxicity to normal tissue is a serious limitation of this treatment modality. The aim of the present study is to investigate the ability of polar steroids from starfish Patiria (=Asterina) pectinifera to enhance the efficacy of radiation therapy in colorectal carcinoma cells. The cytotoxic activity of polar steroids and X-ray radiation against DLD-1, HCT 116, and HT-29 cells was determined by an MTS assay. The effect of compounds, X-ray, and their combination on colony formation was studied using the soft agar method. The molecular mechanism of the radiosensitizing activity of asterosaponin P1 was elucidated by western blotting and the DNA comet assay. Polar steroids inhibited colony formation in the tested cells, and to a greater extent in HT-29 cells. Asterosaponin P1 enhanced the efficacy of radiation and, as a result, reduced the number and size of the colonies of colorectal cancer cells. The radiosensitizing activity of asterosaponin P1 was realized by apoptosis induction through the regulation of anti- and pro-apoptotic protein expression followed by caspase activation and DNA degradation.
Assuntos
Antineoplásicos/farmacologia , Apoptose/genética , Asterina/química , Regulação Neoplásica da Expressão Gênica , Compostos Policíclicos/farmacologia , Radiossensibilizantes/farmacologia , Saponinas/farmacologia , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Caspase 3/genética , Caspase 3/metabolismo , Caspase 9/genética , Caspase 9/metabolismo , Linhagem Celular Tumoral , Terapia Combinada , Células HCT116 , Células HT29 , Humanos , Compostos Policíclicos/química , Compostos Policíclicos/isolamento & purificação , Radiossensibilizantes/química , Radiossensibilizantes/isolamento & purificação , Saponinas/química , Saponinas/isolamento & purificação , Ensaio Tumoral de Célula-Tronco , Raios X , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo , Proteína bcl-X/genética , Proteína bcl-X/metabolismoRESUMO
Six new polyhydroxylated steroids conjugated with taurine, microdiscusols A-F, were isolated from the alcoholic extract of the Arctic starfish Asterias microdiscus. Three of them have been found to have additional sulfate groups in tetracyclic cores. The structures of new compounds were established by 1D and 2D NMR and HRESIMS techniques. The found steroid taurine conjugates resemble, by their structures, salts of bile acids and alcohols of lower vertebrates.