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1.
J Ethnopharmacol ; 303: 115929, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36379416

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Prostate cancer originates from cells inside a gland, which begin to grow out of control. In the world, prostate cancer is the most common cancer in the male population. New therapeutic strategies are needed for this tumor which still has a high mortality. A. arborescens leaves and aerial parts have various ethnopharmacological uses such as anti-spasmodic, and their decoctions were used to resolve urticaria, neuralgia and several lung diseases. Often this species has been also used to treat different inflammatory-related diseases such as cancer. AIM OF THE STUDY: In a continuation of our research on essential oils from medicinal plants, we have selected, two essential oils from Artemisia arborescens L. (Compositae), an aromatic shrub widely used in traditional medicine. We evaluated their pro-apototic effect on androgen-sensitive (LNCaP) and androgen-insensitive (DU-145) human prostate cancer cells. In this study, we also evaluated the anti-Signal transducer and transcription factor 3 (STAT-3) activity of both essential oils in the human prostate cancer cell lines, and the treatment with Tumor necrosis factor (TNF)-Related Apoptosis (TRAIL). MATERIALS AND METHODS: The cells were exposed to essential oils for 72 h and cell viability and cell membrane integrity were evaluated. Genomic DNA and the activity of caspase-3 was tested to confirm the cell death for apoptosis. Western blot analysis was employed to evaluate the expression of Bcl-2, Bax, cleaved caspase-3, cleaved caspase-9, Hsp70, STAT-3 and SOD proteins. Assays to evaluate reactive oxygen species (ROS) and GSH levels were also performed. RESULTS: The results showed the capacity of two essential oils to activate an apoptotic process increasing the inhibition of Hsp70 and STAT-3 protein expression. In addition, our natural products sensitize LNCaP cells to Tumor necrosis factor (TNF)-Related Apoptosis (TRAIL)-induced apoptosis. CONCLUSIONS: In summary, our study provides a further contribution to the hypothesis of the use of essential oils, from traditional medicinal plants, for the treatment of tumors, and suggests that the combination of our samples with other anti-prostate cancer therapies could be used to affect prostate cancer.


Assuntos
Artemisia , Óleos Voláteis , Neoplasias da Próstata , Masculino , Humanos , Caspase 3/metabolismo , Óleos Voláteis/farmacologia , Óleos Voláteis/uso terapêutico , Androgênios/farmacologia , Apoptose , Neoplasias da Próstata/metabolismo , Fatores de Necrose Tumoral/farmacologia , Fatores de Necrose Tumoral/uso terapêutico , Linhagem Celular Tumoral
2.
Chem Biol Interact ; 323: 109075, 2020 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-32229109

RESUMO

The use of orchids in herbal medicine has a very long history. Dendrobium species are known to produce a variety of secondary metabolites such as phenanthrens, bibenzyls, fluorenones and sesquiterpenes, and alkaloids and are responsible for their wide variety of medicinal properties. For decades, bibenzyls, which are the main bioactive components derived from Dendrobium species, have been subjected to extensive investigation as likely candidates for cancer treatment. The present study was undertaken to investigate the effect of moscatilin, a bibenzyl derivative from the orchid Dendrobium loddigesii on human melanoma cells. In A375 cells compound moscatilin showed a clear dose-response relationship in the range of 6.25-50 µM concentrations. In addition, we demonstrated an apoptotic response after treatment of cancer cells with this bibenzyl compound at 6.25 and 12.5 µM concentrations that probably involves PTEN activity, inhibition of Hsp70 expression and reactive oxygen species production. Alternatively, the inhibition of the caspase cascade at higher concentrations, 25 and 50 µM, correlated with additional reactive oxygen species increase, probably switched the mode of moscatilin-induced cell death from apoptosis to necrosis.


Assuntos
Apoptose/efeitos dos fármacos , Compostos de Benzil/uso terapêutico , Dendrobium/química , Melanoma/tratamento farmacológico , Melanoma/patologia , Compostos de Benzil/química , Compostos de Benzil/farmacologia , Caspase 3/metabolismo , Caspase 9/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , DNA de Neoplasias/metabolismo , Glutationa/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Humanos , L-Lactato Desidrogenase/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Proteína X Associada a bcl-2/metabolismo
3.
Molecules ; 26(1)2020 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-33396666

RESUMO

The aim of this study was to determine, first, the chemical composition of Aloysia polystachya (Griseb) Moldenke essential oil, from leaves harvested in central Chile; and second, its antioxidant and cytotoxic activity. Eight compounds were identified via gas chromatography-mass spectrometry (GC-MS) analyses, with the most representative being R-carvone (91.03%), R-limonene (4.10%), and dihydrocarvone (1.07%). For Aloysia polystachya essential oil, antioxidant assays (2,2-diphenyl-1-picrylhydrazyl (DPPH), H2O2, ferric reducing antioxidant power (FRAP), and total reactive antioxidant potential (TRAP)) showed good antioxidant activity compared to commercial antioxidant controls; and anti-proliferative assays against three human cancer cell lines (colon, HT-29; prostate, PC-3; and breast, MCF-7) determined an IC50 of 5.85, 6.74, and 9.53 µg/mL, and selectivity indices of 4.75, 4.12, and 2.92 for HT-29, PC-3, and MCF-7, respectively. We also report on assays with CCD 841 CoN (colon epithelial). Overall, results from this study may represent, in the near future, developments for natural-based cancer treatments.


Assuntos
Antioxidantes/química , Proliferação de Células/efeitos dos fármacos , Monoterpenos Cicloexânicos/análise , Limoneno/análise , Verbenaceae/metabolismo , Linhagem Celular Tumoral , Chile , Cromatografia Gasosa-Espectrometria de Massas , Células HT29 , Humanos , Peróxido de Hidrogênio , Concentração Inibidora 50 , Células MCF-7 , Óleos Voláteis , Células PC-3 , Extratos Vegetais
4.
Artigo em Inglês | LILACS, MTYCI | ID: biblio-1145994

RESUMO

El presente estudio tiene como objetivo explorar las posibles aplicaciones de los extractos de corteza y hoja de Blepharocalyx cruckshanksii como agente citotóxico contra líneas celulares de cáncer in vitro ((MCF-7, PC-3 y HT-29) mediante el uso de ensayo de sulforhodamine B (SRB). El ensayo de citotoxicidad reveló que el extracto de acetato de etilo de la corteza exhibía una actividad anticancerígena marcada. El extracto activo se sometió a un reparto líquido-líquido usando hexano y acetato de etilo para obtener fracciones basadas en su polaridad. Sin embargo, la Fracción 4 (F4) fue identificado como el más efectivo de la serie al mostrar contra todas las líneas celulares de cáncer una citotoxicidad cercana a los agentes antineoplásicos ensayados. Luego, F4 se analizó por cromatografía de gasesespectrometría de masas (GC-MS) para identificar sus componentes principales y relacionar estos componentes con el efecto citotóxico. Los resultados obtenidos indicaron que la corteza de B. cruckshanksii tiene una excelente actividad citotóxica y amerita estudios adicionales para aislar nuevos compuestos para quimioterapia.


The present study aims to explore the potential applications of Blepharocalyx cruckshanksii bark and leaf extracts as a cytotoxic agent against in vitro cancer cell lines (MCF-7, PC-3 and HT-29) by using sulforhodamine B (SRB) assay. The cytotoxicity assay revealed that the ethyl acetate extract from the bark exhibited marked anticancer activity. The active extract was subjected to liquid-liquid partitioning by using hexane and ethyl acetate to obtain fractions based on their polarity. However, Fraction 4 (F4) was identified as the most effective of the series by displaying against all cancer cell lines a cytotoxicity close to antineoplastic agents assayed. Then, F4 was analyzed by gas chromatography­mass spectrometry (GC-MS) to identify their major components and to relate these components to the cytotoxic effect. The results obtained indicated that B. cruckshanksii bark have excellent cytotoxic activity and warrant further studies to isolate novel compounds for chemotherapeutic use.


Assuntos
Humanos , Myrtaceae/química , Citotoxinas , Antineoplásicos , Técnicas In Vitro , Extratos Vegetais , Chile , Cromatografia Gasosa
5.
Phytother Res ; 33(12): 3242-3250, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31489735

RESUMO

Isocordin 1 and a series of 4-oxyalkyl-isocordoin analogues 2-8 were evaluated for their cytotoxicity effect against human melanoma cells (A2058). Analogues 4, 5, and 6 showed a higher inhibitory activity with IC50 values of 12.91 ± 0.031, 24.88 ± 0.013, and 11.62 ± 0.017, respectively. These analogues, 4, 5, and 6, also induced an apoptotic response at 12.5- and 25-µM concentrations. They inhibited the expression of antiapoptotic proteins Bcl-2 and Hsp70, a critical factor that promotes tumour cell survival. In contrast, Bax and caspase-9 expression, and caspase-3 enzyme resulted activated. These results were correlated to a DNA fragmentation typical of apoptosis and an increase of intracellular reactive oxygen species (ROS) levels. Alternatively, at higher concentration (50 µM), when the capacity of the cells to sustain Hsp70 synthesis is reduced, our results seem to indicate that necrosis was induced by a further increase in ROS production. Therefore, the central finding in the present study is that these molecules downregulates Hsp70 expression. Altogether, these results suggest that 4-oxyalkyl-isocordoin analogues 4, 5, and 6 deserve to be deeply investigated for a possible application as Hsp70 inhibitor in the management of melanoma.


Assuntos
Apoptose/efeitos dos fármacos , Catecóis/uso terapêutico , Proteínas de Choque Térmico HSP70/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Catecóis/farmacologia , Humanos
6.
Chem Biol Interact ; 305: 79-85, 2019 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-30935903

RESUMO

Melanoma is a highly invasive cancer that resists most conventional treatments. Therefore, there is an urgent need to identify alternative anticancer agents able to affect new molecular targets. Drimys winteri (Winteraceae) is a medicinal plant, employed in Brazil and many countries, in folk medicine against a variety of ailments, especially for the treatment of fevers, ulcers, pains, affections of respiratory tract and cancers. Previous phytochemical studies have isolated and identified the presence of diverse classes of secondary metabolites in this plant such as sesquiterpenes. In an ongoing to identify new natural anticancer compounds for the treatment and/or prevention of melanoma, we study the effects of Drimys winteri bark ethyl acetate extract and its sesquiterpenes drimenol, nordrimenone, isonordrimenone and polygodial on human melanoma cells. The treatment of melanoma cells with extract, drimenol, isordrimenone and polygodial resulted in a significant reduction in cell viability. But, polygodial showed the highest inhibitory growth activity. In addition, we reported an apoptotic response after treatment with drimenol, isordrimenone and polygodial that probably involves the reduction of Hsp70 expression and reactive oxygen species production. Alternatively, the inhibition of caspase cascade at higher concentrations, correlated with additional reactive oxygen species increase, probably switches natural product-induced cell death from apoptosis to necrosis. Therefore, this evidence provides a scientific support for the anticancer employ of Drimys winteri in traditional medicinal and suggests that active molecules can be considered potential candidates to be tested also in in vivo models, alone or in combination with chemotherapy agents, for the management of melanoma.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Drimys/química , Extratos Vegetais/química , Antineoplásicos Fitogênicos/química , Caspase 3/metabolismo , Linhagem Celular Tumoral , Regulação para Baixo/efeitos dos fármacos , Drimys/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Humanos , Melanoma/metabolismo , Melanoma/patologia , Casca de Planta/química , Casca de Planta/metabolismo , Extratos Vegetais/farmacologia , Plantas Medicinais/metabolismo , Sesquiterpenos Policíclicos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Terpenos/química , Terpenos/farmacologia
7.
Bioorg Med Chem ; 26(14): 3953-3957, 2018 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-29934219

RESUMO

The natural product magnolol (1) and a selection of its bioinspired derivatives 2-5, were investigated by Inverse Virtual Screening in order to identify putative biological targets from a panel of 308 proteins involved in cancer processes. By this in silico analysis we selected tankyrase-2 (TNKS2), casein kinase 2 (CK2) and bromodomain 9 (Brd9) as potential targets for experimental evaluations. The Surface Plasmon Resonance assay revealed that 3-5 present a good affinity for tankyrase-2, and, in particular, 3 showed an antiproliferative activity on A549 cells higher than the well-known tankyrase-2 inhibitor XAV939 used as reference compound.


Assuntos
Antineoplásicos/farmacologia , Compostos de Bifenilo/farmacologia , Lignanas/farmacologia , Tanquirases/antagonistas & inibidores , Algoritmos , Antineoplásicos/síntese química , Antineoplásicos/química , Compostos de Bifenilo/síntese química , Compostos de Bifenilo/química , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Lignanas/síntese química , Lignanas/química , Estrutura Molecular , Proteínas Recombinantes/metabolismo , Relação Estrutura-Atividade , Ressonância de Plasmônio de Superfície , Tanquirases/metabolismo , Termodinâmica , Células Tumorais Cultivadas
8.
Int J Mol Sci ; 19(1)2018 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-29351194

RESUMO

Prostate cancer is one of the most common forms of cancer in men, and research to find more effective and less toxic drugs has become necessary. In the frame of our ongoing program on traditionally used Salvia species from the Mediterranean Area, here we report the biological activities of Salvia aurea, S. judaica and S. viscosa essential oils against human prostate cancer cells (DU-145). The cell viability was measured by 3(4,5-dimethyl-thiazol-2-yl)2,5-diphenyl-tetrazolium bromide (MTT) test and lactate dehydrogenase (LDH) release was used to quantify necrosis cell death. Genomic DNA, caspase-3 activity, expression of cleaved caspase-9, B-cell lymphoma 2 (Bcl-2) and Bcl-2 associated X (Bax) proteins were analyzed in order to study the apoptotic process. The role of reactive oxygen species in cell death was also investigated. We found that the three essential oils, containing caryophyllene oxide as a main constituent, are capable of reducing the growth of human prostate cancer cells, activating an apoptotic process and increasing reactive oxygen species generation. These results suggest it could be profitable to further investigate the effects of these essential oils for their possible use as anticancer agents in prostate cancer, alone or in combination with chemotherapy agents.


Assuntos
Apoptose/efeitos dos fármacos , Medicamentos de Ervas Chinesas/administração & dosagem , Óleos Voláteis/administração & dosagem , Neoplasias da Próstata/tratamento farmacológico , Apoptose/genética , Canfanos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , Medicamentos de Ervas Chinesas/química , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Óleos Voláteis/química , Panax notoginseng , Neoplasias da Próstata/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Espécies Reativas de Oxigênio/metabolismo , Salvia/química , Salvia miltiorrhiza , Proteína X Associada a bcl-2/genética
9.
Food Microbiol ; 68: 61-70, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28800826

RESUMO

The main aim of this work was to evaluate, at pilot scale in an industrial environment, the effects of the biocontrol agent Lactococcus lactis CBM21 and thyme essential oil compared to chlorine, used in the washing step of fresh-cut lamb's lettuce, on the microbiota and its changes in relation to the time of storage. The modification of the microbial population was studied through pyrosequencing in addition to the traditional plate counts. In addition, the volatile molecule and sensory profiles were evaluated during the storage. The results showed no significant differences in terms of total aerobic mesophilic cell loads in relation to the washing solution adopted. However, the pyrosequencing data permitted to identify the genera and species able to dominate the spoilage associations over storage in relation to the treatment applied. Also, the analyses of the volatile molecule profiles of the samples during storage allowed the identification of specific molecules as markers of the spoilage for each different treatment. The sensory analyses after 3 and 5 days of storage showed the preference of the panelists for samples washed with the combination thyme EO and the biocontrol agent. These samples were preferred for attributes such as flavor, acceptability and overall quality. These results highlighted the effect of the innovative washing solutions on the quality of lettuce through the shift of microbiota towards genera and species with lower potential in decreasing the sensory properties of the product.


Assuntos
Bactérias/efeitos dos fármacos , Lactococcus lactis/fisiologia , Óleos Voláteis/farmacologia , Extratos Vegetais/farmacologia , Thymus (Planta)/química , Verduras/microbiologia , Bactérias/classificação , Bactérias/crescimento & desenvolvimento , Bactérias/isolamento & purificação , Biodiversidade , Contaminação de Alimentos/prevenção & controle , Óleos Voláteis/isolamento & purificação , Extratos Vegetais/isolamento & purificação
10.
Nat Prod Commun ; 11(3): 275-8, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27169173

RESUMO

Centaurea is the largest genus within the Asteraceae family. Many members of this genus are used in traditional folk medicine, such as Centaurea pulchella used to treat skin problems such as to resolve the abscess. Although biological activities of many Centaurea species have been investigated in different countries and Turkey, cytotoxic effect of C. patula, C. pulchella and C. tchihatcheffii has not been studied yet. Melanoma is one of the most invasive and deadly forms of skin cancer. Therefore, in an ongoing effort to identify new natural anticancer products for the treatment and/or prevention of melanoma cancer, the present study was undertaken to investigate the effect of these Centaurea species, collected from Central Anatolia region of Turkey on cell growth and death in human melanoma cell line, A375.The results revealed that all extracts were able to inhibit, after 48 h of treatment, the growth of cancer cells, that could be related to an overall action of the phenolic compounds present. In fact, C. pulchella, with the highest level of phenolics, showed a major activity followed by C. patula and C. tchihatcheffii. Our data also demonstrate that these natural products induce apoptotic cell death. In conclusion, the study of plant extracts for their cytotoxic and apoptotic properties has shown that medicinal herbs from Centaurea species might have also importance in the prevention and treatment of melanoma.


Assuntos
Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Centaurea/química , Melanoma/tratamento farmacológico , Linhagem Celular Tumoral , Ensaio Cometa , Humanos , Turquia
11.
Front Microbiol ; 6: 1105, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26528258

RESUMO

AIMS: The aim of this work was to study the responses of Saccharomyces bayanus cells exposed to sub-lethal high-pressure homogenization (HPH) and determine whether the plasmatic membrane can sense HPH in the presence, or absence, of exogenous unsaturated fatty acids (UFAs) in the growth medium. METHODS AND RESULTS: High-pressure homogenization damaged and caused the collapse of cell walls and membranes of a portion of cells; however, HPH did not significantly affect S. bayanus cell viability (less than 0.3 Log CFU ml(-1)). HPH strongly affected the membrane fatty acid (FA) composition by increasing the percentage of total UFA when compared with saturated fatty acids. The gene expression showed that the transcription of OLE1, ERG3, and ERG11 increased after HPH. The presence of exogenous UFA abolished HPH-induced effects on the OLE1 and ERG3 genes, increased the percentage of membrane lipids and decreased the expression of OLE1 and ERG3 within 30 min of treatment. CONCLUSION: The results suggest a key role for UFA in the microbial cell response to sub-lethal stress. In addition, these data provide insight into the molecular basis of the response of S. bayanus to this innovative technology. SIGNIFICANCE AND IMPACT OF THE STUDY: Elucidation of the mechanism of action for sub-lethal HPH will enable the utilization of this technology to modulate the starter performance at the industrial scale.

12.
Int J Mol Sci ; 16(4): 7944-59, 2015 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-25860949

RESUMO

With the aim of identifying novel agents with antigrowth and pro-apoptotic activity on melanoma cancer, the present study was undertaken to investigate the biological activity of the resinous exudate of aerial parts from Psoralea glandulosa, and its active components (bakuchiol (1), 3-hydroxy-bakuchiol (2) and 12-hydroxy-iso-bakuchiol (3)) against melanoma cells (A2058). In addition, the effect in cancer cells of bakuchiol acetate (4), a semi-synthetic derivative of bakuchiol, was examined. The results obtained show that the resinous exudate inhibited the growth of cancer cells with IC50 value of 10.5 µg/mL after 48 h of treatment, while, for pure compounds, the most active was the semi-synthetic compound 4. Our data also demonstrate that resin is able to induce apoptotic cell death, which could be related to an overall action of the meroterpenes present. In addition, our data seem to indicate that the apoptosis correlated to the tested products appears, at least in part, to be associated with an increase of reactive oxygen species (ROS) production. In summary, our study provides the first evidence that P. glandulosa may be considered a source of useful molecules in the development of analogues with more potent efficacy against melanoma cells.


Assuntos
Antineoplásicos/farmacologia , Melanoma/tratamento farmacológico , Extratos Vegetais/farmacologia , Psoralea/química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Fenóis/química , Fenóis/farmacologia , Extratos Vegetais/química , Espécies Reativas de Oxigênio/metabolismo , Resinas Vegetais/química , Resinas Vegetais/farmacologia
13.
Nat Prod Res ; 29(17): 1630-40, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25537231

RESUMO

The objectives of our research were to study the chemical composition and the in vitro anticancer effect of the essential oil of Salvia verbenaca growing in natural sites in comparison with those of cultivated (Sc) plants. The oil from wild (Sw) S. verbenaca presented hexadecanoic acid (23.1%) as the main constituent, while the oil from Sc plants contained high quantities of hexahydrofarnesyl acetone (9.7%), scarce in the natural oil (0.7%). The growth-inhibitory and proapoptotic effects of the essential oils from Sw and Sc S. verbenaca were evaluated in the human melanoma cell line M14, testing cell vitality, cell membrane integrity, genomic DNA fragmentation and caspase-3 activity. Both the essential oils were able to inhibit the growth of the cancer cells examined inducing also apoptotic cell death, but the essential oil from cultivated samples exhibited the major effects.


Assuntos
Antineoplásicos Fitogênicos/química , Óleos Voláteis/química , Óleos de Plantas/química , Salvia/química , Apoptose , Caspase 3/metabolismo , Linhagem Celular Tumoral/efeitos dos fármacos , Fragmentação do DNA , Humanos , Melanoma/patologia , Ácido Palmítico/química , Ácido Palmítico/isolamento & purificação , Terpenos/química , Terpenos/isolamento & purificação
14.
Mol Nutr Food Res ; 57(5): 840-53, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23322423

RESUMO

SCOPE: Exposure of the breast to estrogens and other sex hormones is an important cancer risk factor and estrogen receptor downregulators are attracting significant clinical interest. Epigallocatechin gallate (EGCG), a polyphenolic compound found in green tea, has gained considerable attention for its antitumor properties. Here we aimed to investigate the molecular mechanisms through which EGCG regulates ER-α expression in ER+ PR+ breast cancer cells. MATERIAL AND METHODS: Western blotting analysis, real-time PCR, and transient transfections of deletion fragments of the ER-α gene promoter show that EGCG downregulates ER-α protein, mRNA, and gene promoter activity with a concomitant reduction of ER-α genomic and nongenomic signal. These events occur through p38(MAPK) /CK2 activation, causing the release from Hsp90 of progesterone receptor B (PR-B) and its consequent nuclear translocation as evidenced by immunofluorescence studies. EMSA, and ChIP assay reveal that, upon EGCG treatment, PR-B is recruited at the half-PRE site on ER-α promoter. This is concomitant with the formation of a corepressor complex containing NCoR and HDAC1 while RNA polymerase II is displaced. The events are crucially mediated by PR-B isoform, since they are abrogated with PR-B siRNA. CONCLUSION: Our data provide evidence for a mechanism by which EGCG downregulates ER-α and explains the inhibitory action of EGCG on the proliferation of ER+ PR+ cancer cells tested. We suggest that the EGCG/PR-B signaling should be further exploited for clinical approach.


Assuntos
Neoplasias da Mama/genética , Catequina/análogos & derivados , Regulação para Baixo , Receptor alfa de Estrogênio/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias da Mama/patologia , Catequina/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Imunoprecipitação da Cromatina , Receptor alfa de Estrogênio/metabolismo , Feminino , Proteínas de Choque Térmico HSP90/genética , Proteínas de Choque Térmico HSP90/metabolismo , Histona Desacetilase 1/genética , Histona Desacetilase 1/metabolismo , Humanos , Correpressor 1 de Receptor Nuclear/genética , Correpressor 1 de Receptor Nuclear/metabolismo , Regiões Promotoras Genéticas , RNA Polimerase II/genética , RNA Polimerase II/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais , Chá/química
15.
Mol Nutr Food Res ; 56(11): 1655-64, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22976781

RESUMO

SCOPE: Green tea and its major constituent epigallocatechin gallate (EGCG) have been extensively studied as potential treatment for a variety of diseases. We assessed the influence of EGCG on male fertilizing potential by analyzing different features of human sperm involved in capacitation process. METHODS AND RESULTS: Using human normozoospermic samples, we evaluated the effect of EGCG (2 µM, 20 µM, 60 µM) on sperm activities. Our results showed that lower doses of EGCG (from 2 to 20 µM) increased cholesterol efflux and tyrosine phosphorylation through the estrogen receptor (ER), since ICI 182,780, a specific ER antagonist, abrogated 20 µM EGCG effects. Besides, we evidenced that EGCG at similar concentrations, increased sperm motility, viability, and phosphorylation of proteins controlling cell survival such as Bcl2, Akt, and Src, via ER. Furthermore, we observed reduction of triglycerides content, induction of lipase, as well as the G6PDH activity. These results address to an increase in energy expenditure. On the contrary, treatment of 60 µM EGCG produced opposite effects that still appear after ICI cotreatment. CONCLUSION: These results provide a novel mechanism involving ERs through which low doses of EGCG exerted benefits to sperm physiology, also detected data evidence the adverse action of high EGCG concentrations probably related to its prooxidant and antiestrogenic potential.


Assuntos
Catequina/análogos & derivados , Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Catequina/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Colesterol/metabolismo , Relação Dose-Resposta a Droga , Estradiol/análogos & derivados , Estradiol/farmacologia , Fulvestranto , Glucose/metabolismo , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Fosforilação/efeitos dos fármacos , Proteínas/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Receptores de Estrogênio/antagonistas & inibidores , Receptores de Estrogênio/metabolismo , Motilidade dos Espermatozoides/efeitos dos fármacos , Chá/química , Triglicerídeos/metabolismo , Tirosina/metabolismo , Quinases da Família src/metabolismo
16.
Planta Med ; 78(15): 1651-60, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22965548

RESUMO

A phytochemical investigation of acetone and chloroform extracts of the aerial parts of Onopordum cynarocephalum Boiss. et Blanche was carried out. It led to the isolation of two new sesquiterpenes, the elemane aldehyde (2) and the eudesmane (11), together with 15 known compounds: two lignans (1 and 15) and 13 sesquiterpenes (3-10, 12-14, 16, 17). The structures were elucidated by spectroscopic analyses, especially 1D and 2D NMR spectra. The anti-growth effect against three human melanoma cell lines, M14, A375, and A2058, of the different extracts and compounds of O. cynarocephalum was also investigated. Among them, the chloroform extract exhibited the strongest biological activity, while the most active compounds were the lignan arctigenin (1), and the sesquiterpenes, compounds 3, 5, and 6 belonging to the elemane type, and 7 belonging to the eudesmane type. Our data also demonstrate that acetone and chloroform extracts induce, in the A375 cell line, apoptotic cell death that could be related to an overall action of the compounds present, but in particular to the lignans arctigenin (1) and the sesquiterpenes compounds 3-8 and 16. In fact, these molecules were able to induce a high DNA fragmentation, correlated to a significant increase of the caspase-3 enzyme activity. Furthermore, apoptosis appears to be mediated, at least in part, via PTEN activity and the inhibition of Hsp70 expression.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Furanos/farmacologia , Lignanas/farmacologia , Onopordum/química , Extratos Vegetais/farmacologia , Sesquiterpenos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Caspase 3/efeitos dos fármacos , Caspase 3/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , Relação Dose-Resposta a Droga , Furanos/química , Furanos/isolamento & purificação , Proteínas de Choque Térmico HSP70/efeitos dos fármacos , Proteínas de Choque Térmico HSP70/metabolismo , Humanos , Concentração Inibidora 50 , Lignanas/química , Lignanas/isolamento & purificação , Estrutura Molecular , Sesquiterpenos Monocíclicos , PTEN Fosfo-Hidrolase/efeitos dos fármacos , PTEN Fosfo-Hidrolase/metabolismo , Componentes Aéreos da Planta/química , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Sesquiterpenos de Eudesmano/química , Sesquiterpenos de Eudesmano/isolamento & purificação , Sesquiterpenos de Eudesmano/farmacologia
17.
J Pharm Pharmacol ; 63(9): 1219-29, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21827495

RESUMO

OBJECTIVES: This study was designed to investigate the potential protective effect of a methanolic extract of Peumus boldus leaves on UV light and nitric oxide (NO)-mediated DNA damage. In addition, we investigated the growth inhibitory activity of this natural product against human melanoma cells (M14). METHODS: Boldine, catechin, quercetin and rutin were identified using a HPLC method. The extract was incubated with plasmid DNA and, before irradiating the samples with UV-R, H(2) O(2) was added. For analysis of DNA single-strand breaks induced by NO, the experiments were performed by incubating the extract with Angeli's salt. In the study on M14 cell line, cell viability was measured using MTT assay. Release of lactate dehydrogenase, a marker of membrane breakdown, was also measured. For the detection of apoptosis, the evaluation of DNA fragmentation (COMET assay) and caspase-3 activity assay were employed. The expression of heat shock protein 70 (Hsp70) was detected by Western blot analysis. Generation of reactive oxygen species was measured by using a fluorescent probe. KEY FINDINGS: The extract (demonstrating the synergistic effect of the constituents boldine and flavonoids), showed a protective effect on plasmid DNA and selectively inhibited the growth of melanoma cells. But a novel finding was that apoptosis evoked by this natural product in M14 cells, appears to be mediated, at least in part, via the inhibition of Hsp70 expression, which may be correlated with a modulation of redox-sensitive mechanisms. CONCLUSIONS: These results confirm the promising biological properties of Peumus boldus and encourage in-vivo investigations into its potential anti-cancer activity.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Dano ao DNA/efeitos dos fármacos , Proteínas de Choque Térmico HSP70/antagonistas & inibidores , Melanoma/prevenção & controle , Peumus/química , Extratos Vegetais/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proteínas de Choque Térmico HSP70/metabolismo , Humanos , Melanoma/metabolismo , Óxido Nítrico/efeitos adversos , Oxirredução , Fitoterapia , Extratos Vegetais/uso terapêutico , Folhas de Planta , Plasmídeos/efeitos dos fármacos , Plasmídeos/genética , Plasmídeos/efeitos da radiação , Raios Ultravioleta/efeitos adversos
18.
Nat Prod Commun ; 6(7): 1023-6, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21834249

RESUMO

Salvia verbenaca L. (syn. S. minore) is a perennial herb known in the traditional medicine of Sicily as "spaccapetri" and is used to resolve cases of kidney stones, chewing the fresh leaves or in decoction. The chemical composition of the essential oil obtained from aerial parts of S. verbenaca collected in Piano Battaglia (Sicily) on July 2009, was analyzed by GC and GC-MS. The oil was strongly characterized by fatty acids (39.5%) and carbonylic compounds (21.2%), with hexadecanoic acid (23.1%), (Z)-9-octadecenoic acid (11.1%) and benzaldehyde (7.3%) as the main constituents. The in vitro activity of the essential oil against some microorganisms in comparison with chloramphenicol by the broth dilution method was determined. The oil exhibited a good activity as inhibitor of growth of Gram + bacteria.


Assuntos
Antibacterianos/isolamento & purificação , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Óleos de Plantas/química , Óleos de Plantas/farmacologia , Salvia/química , Antibacterianos/química , Antibacterianos/farmacologia , Ácidos Carboxílicos/química , Ácidos Carboxílicos/isolamento & purificação , Ácidos Carboxílicos/farmacologia , Ácidos Graxos/química , Ácidos Graxos/isolamento & purificação , Ácidos Graxos/farmacologia , Cromatografia Gasosa-Espectrometria de Massas , Testes de Sensibilidade Microbiana , Componentes Aéreos da Planta/química , Sicília
19.
Nat Prod Commun ; 5(7): 1127-32, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20734956

RESUMO

Genista species (family Leguminosae) show interesting biological properties. In this paper we describe the biological activity of the essential oils extracted from the aerial parts of G. sessilifolia DC. and G. tinctoria L. against M14 human melanoma cells, testing several biochemical parameters, such as cell vitality, cell membrane integrity and genomic DNA fragmentation. In addition, we report for the first time the study of the composition of the essential oil obtained from G. tinctoria. The most abundant components of the oil were carbonylic compounds such as (E)-beta-ionone (9.1%), dihydroactinidiolide (7.3%), nonanal (5.1%) and hexahydrofarnesylacetone (4.3%). The essential oils from aerial parts of both G. sessilifolia and G. tinctoria showed interesting potential anticancer activity, suggesting the presence of active compounds.


Assuntos
Genista/química , Melanoma/tratamento farmacológico , Óleos Voláteis/química , Óleos Voláteis/uso terapêutico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos
20.
South Med J ; 103(1): 90-2, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19996849

RESUMO

A healthy 33-year-old woman consumed a slimming product containing a mixture of herbal remedies without seeking medical advice. Two months later, the patient had hemorrhagic cystitis and discontinued the herbal product. Symptoms spontaneously remitted in a few days. Four months later, she took the same herbal remedy and the hemorrhagic cystitis reappeared. She then consulted her general practitioner. A urine culture test was negative, and the patient was advised to discontinue the herb intake. Again, the cystitis resolved within a week. The product involved contains a mixture of herbs, some of which have been associated with adverse effects that might account for the symptoms reported in this case.


Assuntos
Cistite/induzido quimicamente , Hematúria/induzido quimicamente , Extratos Vegetais/efeitos adversos , Adulto , Ananas/efeitos adversos , Feminino , Fucus , Humanos , Juniperus/efeitos adversos , Taraxacum/efeitos adversos
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