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1.
Mar Drugs ; 19(2)2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33499163

RESUMO

Marine plants have become an inexhaustible reservoir of new phytopharmaceuticals for cancer treatment. We demonstrate in vitro/in vivo antitumor efficacy of a standardized polyphenol extract from the marine angiosperm Thalassia testudinum (TTE) in colon tumor cell lines (RKO, SW480, and CT26) and a syngeneic allograft murine colorectal cancer model. MTT assays revealed a dose-dependent decrease of cell viability of RKO, CT26, and SW480 cells upon TTE treatment with IC50 values of, respectively, 175, 115, and 60 µg/mL. Furthermore, TTE significantly prevented basal and bFGF-induced angiogenesis in the chicken chorioallantoic membrane angiogenesis assay. In addition, TTE suppressed bFGF-induced migration of endothelial cells in a wound closure assay. Finally, TTE treatment abrogated CT26 colorectal cancer growth and increased overall organism survival in a syngeneic murine allograft model. Corresponding transcriptome profiling and pathway analysis allowed for the identification of the mechanism of action for the antitumor effects of TTE. In line with our in vitro/in vivo results, TTE treatment triggers ATF4-P53-NFκB specific gene expression and autophagy stress pathways. This results in suppression of colon cancer cell growth, cell motility, and angiogenesis pathways in vitro and in addition promotes antitumor immunogenic cell death in vivo.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Movimento Celular/efeitos dos fármacos , Neoplasias Colorretais/patologia , Hydrocharitaceae , Morte Celular Imunogênica/efeitos dos fármacos , Neovascularização Patológica/patologia , Extratos Vegetais/uso terapêutico , Animais , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Autofagia/efeitos dos fármacos , Autofagia/fisiologia , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Humanos , Hydrocharitaceae/química , Morte Celular Imunogênica/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/metabolismo , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
2.
J Pharm Pharmacol ; 70(11): 1553-1560, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30159909

RESUMO

OBJECTIVES: Reported antioxidant, anti-inflammatory and neuroprotective properties for one aqueous-ethanolic extract from Thalassia testudinum which grows in the Caribbean Sea compelled us to explore about extract cytotoxic effects. METHODS: Cell viability was assayed on tumour (HepG2, PC12, Caco-2 and 4T1) and non-tumour (VERO, 3T3, CHO, MCDK and BHK2) cell lines. The extract effects upon primary cultures of rat and human hepatocytes and human lymphocytes were assayed. KEY FINDINGS: The extract exhibited cytotoxicity against cancer cells compared to normal cells, and the IC50 values were 102 µg/ml for HepG2, 135 µg/ml for PC12, 165 µg/ml for Caco-2 and 129 µg/ml for 4T1 cells after 48 h, whereas IC50 could not be calculated for normal cells. Additional data from a high-content screening multiparametric assay indicated that after 24-h exposure, the extract (up to 100 µg/ml) induced death in HepG2 cells through oxidative stress-associated mechanism, DNA damage and hypercalcaemia. Comet assay corroborated extract-induced DNA damage. CONCLUSIONS: Thalassia testudinum extract is more cytotoxic and produced more DNA damage on human hepatoma cells than to other non-tumour cells. A possible mechanism is suggested for extract-induced cytotoxicity based on oxidative stress, nuclear damage and hypercalcaemia in HepG2 cells. T. testudinum may be a source for antitumour agents.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Etanol/química , Neoplasias/tratamento farmacológico , Extratos Vegetais/farmacologia , Solventes/química , Água/química , Adulto , Animais , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/toxicidade , Células CACO-2 , Região do Caribe , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Células Hep G2 , Humanos , Hydrocharitaceae , Concentração Inibidora 50 , Linfócitos/efeitos dos fármacos , Linfócitos/patologia , Masculino , Neoplasias/patologia , Células PC12 , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/toxicidade , Cultura Primária de Células , Ratos , Ratos Sprague-Dawley
3.
Rev. biol. trop ; Rev. biol. trop;64(4): 1527-1535, oct.-dic. 2016. ilus
Artigo em Inglês | LILACS | ID: biblio-958232

RESUMO

Abstract:The marine angiosperm Thalassia testudinum, commonly known as turtle grass, is a dominant sea- grass that grows in the Caribbean Sea shelf associated to Syringodium filiforme. The hydroalcoholic extract of T. testudinum is rich in polyphenols; the most abundant metabolite in this extract is thalassiolin B, a glycosilated flavonoid with skin damage repairing properties, and antioxidant capacity among others. The present study aimed at generating information about the seasonal behavior of secondary metabolites, as well as to study the antioxidant capacity of the T. testudinum leaves extract, collected monthly during 2012 from the Northeast coastline of Havana, Cuba. For this study, spectrophotometric methods were used to determine the concentrations of polyphenols, flavonoids, anthocyanins, soluble carbohydrates and proteins, chlorophylls a and b, and antioxidant activity of the extracts. In general, results demonstrated seasonal variations of the analyzed parameters. Extracts prepared from the vegetal material collected in October and November showed the highest values of polyphenols (58.81 ± 1.53 and 52.39 ± 0.63 mg/g bs, respectivally) and flavonoids (44.12 ± 1.30 and 51.30 ± 0.67 mg/g dw, respectively). On the contrary, the lowest values of polyphenols were found in extracts of leaves collected in July and August (15.51 ± 0.84 and 13.86 ± 0.48 mg/g, respectively). In accordance with these results, the lower value of Inhibitory Concentration (IC50) was obtained to get a 50 % of maximal effect on free radical scavenging activity with the extracts prepared from leaves collected in October and November, and less significant IC50 was obtained from the extract prepared from leaves collected in August (5.63 mg/mL). A negative correlation (r= -0.694) was observed in this study between the content of polyphenols and the IC50 necessary to get the half of its antioxidant maximal effect. The high correspondence between the maximum values of polyphenols, flavonoids, carbohydrates and proteins in October and November, revealed a close relationship between these metabolites found in the extract of T. testudinum. Our hypothesis about the annual variation in the concentration of these metabolites was validated; and these results will support the correct harvesting of T. testudinum leaves for biotechnology and industrial purposes. Rev. Biol. Trop. 64 (4): 1527-1535. Epub 2016 December 01.


Resumen:La angiosperma marina Thalassia testudinum, comúnmente conocida como "hierba tortuga", es un pasto marino dominante que crece en el Mar Caribe asociada a Syringodium filiforme. El extracto hidroalcohólico de T. testudinum es rico en polifenoles; el metabolito más abundante en este extracto es thalassiolina B, un flavonoide glicosilado con propiedades para la reparación de daños en la piel y la capacidad antioxidante, entre otros. El objetivo del presente estudio fue conocer el comportamiento estacional de los metabolitos secundarios, así como la capacidad antioxidante del extracto de hojas de T. testudinum recolectadas mensualmente durante el 2012, en la costa noreste de La Habana, Cuba. Para este estudio fueron empleados métodos espectrofotométricos para la determinación de la concentración de polifenoles, flavonoides, carbohidratos y proteínas solubles, clorofilas a y b y la actividad antioxidante del extracto. En sentido general, los resultados demostraron las variaciones estacionales de los parámetros analizados; los extractos preparados a partir de material vegetal recolectado en octubre y noviembre mostraron los mayores valores de polifenoles y flavonoides (44.12 ± 1.30 y 51.30 ± 0.67 mg/g bs respectivamente) y se encontraron los valores más bajos en los extractos de hojas recolectadas en julio y agosto. (15.51 ± 0.84 y 13.86 ± 0.48 mg/g respectivamente). De acuerdo con los resultados, se obtuvo el valor más bajo de la concentración inhibitoria (CI50 ) necesaria para obtener un 50 % de efecto máximo en la actividad de captación de radicales libres con los extractos preparados a partir de las hojas recolectadas en octubre y noviembre y la CI50 menos significativa se obtuvo a partir del extracto preparado a partir de las hojas recolectadas en agosto (5.63 mg/ml). Se observó una correlación negativa (r= -0,694) entre el contenido de polifenoles y la CI50 necesaria para obtener la mitad del efecto antioxidante máximo. La alta correspondencia que existe entre los valores máximos de polifenoles, flavonoides, carbohidratos y proteínas en octubre y noviembre reveló una estrecha relación entre estos metabolitos, encontrados en el extracto de T. testudinum. La hipótesis de la variación anual de la concentración de estos metabolitos fue validada. Estos resultados se tendrán en cuenta con el fin de seleccionar el momento de recolecta de las hojas de T. testudinum para su uso con fines biotecnológicos e industriales.


Assuntos
Estações do Ano , Extratos Vegetais/química , Hydrocharitaceae/química , Valores de Referência , Espectrofotometria/métodos , Fatores de Tempo , Flavonoides/análise , Carboidratos/análise , Clorofila/análise , Polifenóis/análise , Antocianinas/análise , Antioxidantes/análise
4.
Rev Biol Trop ; 64(4): 1527-35, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29465915

RESUMO

The marine angiosperm Thalassia testudinum, commonly known as turtle grass, is a dominant seagrass that grows in the Caribbean Sea shelf associated to Syringodium filiforme. The hydroalcoholic extract of T. testudinum is rich in polyphenols; the most abundant metabolite in this extract is thalassiolin B, a glycosilated flavonoid with skin damage repairing properties, and antioxidant capacity among others. The present study aimed at generating information about the seasonal behavior of secondary metabolites, as well as to study the antioxidant capacity of the T. testudinum leaves extract, collected monthly during 2012 from the Northeast coastline of Havana, Cuba. For this study, spectrophotometric methods were used to determine the concentrations of polyphenols, flavonoids, anthocyanins, soluble carbohydrates and proteins, chlorophylls a and b, and antioxidant activity of the extracts. In general, results demonstrated seasonal variations of the analyzed parameters. Extracts prepared from the vegetal material collected in October and November showed the highest values of polyphenols (58.81 ± 1.53 and 52.39 ± 0.63 mg/g bs, respectivally) and flavonoids (44.12 ± 1.30 and 51.30 ± 0.67 mg/gdw, respectively). On the contrary, the lowest values of polyphenols were found in extracts of leaves collected in July and August (15.51 ± 0.84 and 13.86 ± 0.48 mg/g,respectively). In accordance with these results, the lower value of Inhibitory Concentration (IC50) was obtained to get a 50 % of maximal effect on free radical scavenging activity with the extracts prepared from leaves collected in October and November, and less significant IC50 was obtained from the extract prepared from leaves collected in August (5.63 mg/mL). A negative correlation (r= -0.694) was observed in this study between the content of polyphenols and the IC50 necessary to get the half of its antioxidant maximal effect. The high correspondence between the maximum values of polyphenols, flavonoids, carbohydrates and proteins in October and November, revealed a close relationship between these metabolites found in the extract of T. testudinum. Our hypothesis about the annual variation in the concentration of these metabolites was validated; and these results will support the correct harvesting of T. testudinum leaves for biotechnology and industrial purposes.


Assuntos
Hydrocharitaceae/química , Extratos Vegetais/química , Estações do Ano , Antocianinas/análise , Antioxidantes/análise , Carboidratos/análise , Clorofila/análise , Colorimetria/métodos , Flavonoides/análise , Hydrocharitaceae/metabolismo , Folhas de Planta/química , Polifenóis/análise , Valores de Referência , Espectrofotometria/métodos , Fatores de Tempo
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