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This study evaluated the chemical composition and anti-proliferative activity of essential oils (EOs) obtained by hydrodistillation from seven medicinal plants from Cachicadán, La Libertad Región, Perú. Limonene (0.64 to 44.43%) and linalool (0.36 to 2.12%) were identified in all EOs by gas chromatography coupled to mass spectrometry analysis. The major components (relative intensity ≥ 10%) were cis-dihydro carvone, carvone, and cis-piperitone epoxide for Minthostachys mollis leaves; ß-pinene, limonene, and ledol for Lepechinia heteromorpha leaves; limonene, neral, and geranial for Aloysia citriodora, both leaves and flowers; α-pinene, and limonene for Myrcianthes myrsinoides leaves; and α-pinene, ß-myrcene, and (E)-ß-Ocimene for Dalea carthagenensis leaves. Constituted by (Z)-ß-ocimene, dihydrotagetone, (Z)-tagetone, and car-3-en-2-one, EO of Tagetes minuta leaves induced an irreversible cytostatic effect against MCF-7 human breast tumor cells. Further in vivo studies must be carried out to establish the safe and efficient dose of T. minuta EO as adjuvant treatment in oncological therapies.
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Sterile bracts can represent 80% of Araucaria angustifolia pinecone and are a rich source of phenolic compounds. This study aimed to optimize the extraction of the phenolic compounds from Araucaria angustifolia bracts using response surface methodology; the bioactivity properties were also investigated. The effects of the ethanol concentration, solute/solvent ratio, and temperature in relation to the phenolic composition and antioxidant activity were evaluated. The quantification and identification of the individual phenolic compounds (using high-performance liquid chromatography) and their bioactivity were evaluated. The optimized extraction conditions, which detected gallic acid, catechin, epicatechin, quercetin, and kaempferol, were obtained using 60% ethanol at a ratio of 1:38 (w/v) and a temperature of 80 °C. The extract showed high levels of phenolic classes and antioxidant activity. The extract also showed an inhibitory activity for pathogenic (approximately 80%, 10,000 µg/mL) and lactic acid (27.9%, 15,000 µg/mL) bacteria strains. The α-glucosidase inhibitory activity was approximately ten times greater than acarbose, demonstrating its high antiglycemic potential. No antioxidant and anti-inflammatory cellular activity were determined; however, a high cytotoxicity for non-tumor cells and the antiproliferative activity against the tumor cells were observed. Overall, the phenolic extract showed promising action in relation to the fight against the diseases related to oxidative stress and, hopefully, the application of the safe concentrations of the extract, based on bioavailability assays, can be verified.
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Phenolic compounds in crude extracts were obtained from defatted sunflower seed flour using sodium bisulfite and ethanol solutions as extracting agents. The antioxidant, antimicrobial, anti-proliferative, and DNA protective activities of the phenolic compounds in crude extract were analyzed. The phenolic compound contents were determined as chlorogenic acid (CGA) equivalent, presenting 11.57 and 15.44 g CGA eq/100g regarding the sodium bisulfite extract and ethanolic extract, respectively. The ORAC, DPPH, and ABTS methods were used to evaluate antioxidant activity. Both extracts presented antioxidant properties, considering that the ethanolic extract demonstrated higher values (EC50 0.36 g extract/g DPPHâ¢). The antimicrobial action was analyzed as to the minimal inhibitory concentration (MIC) and the minimal bactericidal concentration (MBC) of 4 kinds of bacteria (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Bacillus subtilis). The ethanolic extract was effective against all of these microorganisms, out of which E. coli was the most sensitive, with a MIC of 11.6 mg CGA/mL. The ethanolic extract presented DNA protective activity without cytotoxic activity concerning in vitro anti-proliferative assay. These findings can be considered as initial evidence of the potential use of phenolic compounds obtained from sunflower seed flour as natural additives in the food industry.
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Rosemary (Rosmarinus officinalis) is a culinary and medicinal plant used in food and pharmaceutical industry. The wide range of biological activities is mainly related to phenolic and terpenic compounds; like carnosic acid (CA), carnosol (CS) and rosmarinic acid (RA), mainly reported in rosemary leaf extracts, and recently described in rosemary callus extracts. The aim of this work was to investigate the chemical profile of rosemary cell lines and evaluate their antiproliferative potential against human HT-29 colorectal cancer cell lines. For this purpose, rosemary leaf explants were dedifferentiated on MS medium and added with 2, 4-D (2, 4-dichlorophenoxyacetic acid; 2 mg/L) and BAP (6-benzylaminopurine; 2 mg/L). Cell aggregates were separated according to colour and three rosemary cell lines cultures were established: green (RoG), yellow (RoY) and white (RoW). The chemical profile of rosemary cell lines extracts was characterized by combining HPLC and GC platforms coupled to HR-MS/MS. The antiproliferative activity against HT-29 cell line was analyzed with MTT assay. A total of 71 compounds, including hydroxycinnamic acid and hydroxybenzoic acid derivatives, flavonoids, phenolic di- and triterpenes, as well as relevant unsaturated fatty acids and their esters, phytosterols, and carotenoids were tentatively identified in the extract of the target cell lines. The antiproliferative activity test against HT-29 cell using the MTT assay revealed that the viability of HT-29 colon cancer cells was affected after treatment with the RoW extract (IC50 of 49.63 µg/mL) at 48 h. These results showed that rosemary cell lines can also accumulate other bioactive phytochemicals with demonstrated antiproliferative potential.
Assuntos
Neoplasias do Colo , Rosmarinus , Cromatografia Líquida de Alta Pressão , Neoplasias do Colo/tratamento farmacológico , Células HT29 , Humanos , Extratos Vegetais/farmacologia , Espectrometria de Massas em TandemRESUMO
The sterol 3ß,5α,6ß,7α-tetrahydroxyergosta-8(14),22-diene was obtained from bio-guided fractioning of the chloroform extract of 50 L of liquid culture of Acremonium persicinum. This fungal strain was selected because of its anti-proliferative activity against solid human tumour cell lines (GI50 ≤ 50 µg/mL) in a bio-prospective study of fungi isolated from plant material, sediment and water samples obtained from alkaline lakes Alchichica and Atexcac in Puebla, Mexico. This compound showed GI50 (µM) values of: 16, 24, 18, 15 and 12 against tumour cell lines A-549, HBL-100, HeLa, T-47D and WiDr respectively. GI50 effects against tumour lines T-47D and WiDr were found to be greater than the clinically used drugs Etoposide and Cisplatin. Because of this, the results obtained support the pharmacological importance of the microorganisms that develop in these ecosystems and strengthen the non-invasive bio-prospection studies that our work group has developed in recent years.
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Acremonium , Antineoplásicos/farmacologia , Lagos , Acremonium/química , Antineoplásicos/isolamento & purificação , Linhagem Celular Tumoral , Humanos , Lagos/microbiologia , MéxicoRESUMO
INTRODUCCIÓN: la formación de acrilamida (AA) en alimentos que fueron sometidos a tratamiento térmico, fue un descubrimiento inesperado en abril del 2002 por la Universidad de Estocolmo y la Administración Nacional de Alimentos de Suecia (NFA). Esta sustancia potencialmente tóxica y su metabolito glicidamida (GA) se forman en muchos alimentos cocidos a temperaturas elevadas. OBJETIVO: en virtud de que no hay estudios de estas sustancias químicas, en células vegetales, el objetivo fue comprobar el efecto genotóxico de la AA y GA en células de Allium cepa. MATERIALY MÉTODO: se determinó el efecto citotóxico a través del crecimiento de la raíz, actividad proliferativa y las aberraciones cromosómicas de la AA y GA en células meristemáticas de Allium cepa, expuestas a diferentes tiempos y concentraciones, evaluando el crecimiento de la raíz, la actividad proliferativa y las aberraciones cromosómicas. RESULTADOS: GA causa una inhibición del crecimiento de la raíz cuya intensidad depende de la concentración en un medio dado y la AA no muestra diferencias estadísticamente significativas respecto al control. La GA bloquea el ciclo de división celular en una etapa previa a la mitosis y no ocurre lo mismo con la AA. En cuanto a los efectos clastogénicos la GA induce estos efectos en las raíces meristemáticas de Allium cepa, en cambio la AA no los produce. CONCLUSIONES: en este estudio, aunque las concentraciones de AA y GA son mucho más altas que lo niveles de exposición alimentaria en humanos, la GA fue claramente genotóxica para células vegetales, a una determinada concentración, con una marcada citotoxicidad. Por lo tanto, nos permitió distinguir las diferencias entre AA y GA.
INTRODUCTION: the formation of acrylamide (AA) in foods that were sometimes heat treated was an unexpected discovery in April 2002, by Stockholm University and the Swedish National Food Administration (NFA). This potentially toxic substance and its metaboliteglycidamide (GA) form in many foods cooked at elevated temperatures. OBJECTIVES: because there are no studies of these chemicals, in plant cells, the objective was to verify the genotoxic effect of AA and GA in Allium cepa cells MATERIAL AND METHODS: to determine the cytotoxic effect through root growth, proliferative activity and chromosomal aberrations of acrylamide and glycidamide in Allium strain meristematic cells exposed to different times and antibodies, to evaluate root growth, proliferative activity and chromosomal aberrations. RESULTS: GA causes an inhibition of root growth whose intensity depends on the concentration in a given medium and AA does not show statistically significant differences with respect to the control. GA blocks the cell division cycle at a stage prior to mitosis, and the same does not occur with AA. Regarding the clastogenic effects, GA induces these effects in the meristematic roots of Allium strain, whereas AA does not produce them. CONCLUSIONS: in this study, although AA and GA concentrations are much higher than levels of dietary exposure in humans, GA was clearly genotoxic to plant cells, at a certain concentration, with marked cytotoxicity. For the therefore, it allowed us to distinguish the differences between AA and GA.
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Allium , Tratamento Térmico , Acrilamida , Genotoxicidade , AlimentosRESUMO
BACKGROUND: Viscum album L. (Santalaceae), commonly known as mistletoe, is a hemiparasitic plant traditionally used in complementary cancer treatment. Its antitumor potential is mostly attributed to the presence of aqueous soluble metabolites; however, the use of ethanol as solvent also permits the extraction of pharmacological compounds with antitumor potential. The clinical efficacy of mistletoe therapy inspired the present work, which focuses on ethanolic extracts (V. album "mother tinctures", MT) prepared from different host trees. METHODS: Samples from three European subspecies (album, austriacum, and abietis) were harvested, and five different V. album-MT strains were prepared. The following phytochemical analyses were performed: thin layer chromatography (TLC), high-performance liquid chromatography (HPLC) and liquid chromatography-high resolution mass spectrometry (LC-HRMS). The proliferation assay was performed with WST-1 after incubation of tumor (Yoshida and Molt-4) and fibroblast cell lines (NIH/3 T3) with different MT concentrations (0.5 to 0.05% v/v). The cell death mechanism was investigated by flow cytometry (FACS) using Annexin V-7AAD. RESULTS: Chemical analyses of MT showed the presence of phenolic acids, flavonoids and lignans. The MT flavonoid and viscotoxin contents (mg/g fresh weight) were highest in Quercus robur (9.67 ± 0.85 mg/g) and Malus domestica (3.95 ± 0.58 mg/mg), respectively. The viscotoxin isoform proportions (% total) were also different among the VA subspecies with a higher content of A3 in V. album growing on Abies alba (60.57 ± 2.13). The phytochemical compounds as well as the viscotoxin contents are probably related to the antitumor effects of MT. The cell death mechanisms evaluated by colorimetric and FACS methodologies involved necrotic damage, which was host tree-, time- and dose- dependent, with different selectivity to tumor cells. Mother tincture from V. album ssp. abietis was the most effective at inducing in vitro cellular effects, even when incubated at the smallest concentration tested, probably because of the higher content of VT A3. CONCLUSION: Our results indicate the promising antitumor potential of Viscum album ethanolic extracts and the importance of botanical and phytochemical characterization for in vitro anti-proliferative effects.
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Antineoplásicos/química , Antineoplásicos/farmacologia , Erva-de-Passarinho/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Viscum album/química , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Técnicas In VitroRESUMO
The research of natural products has allowed for the discovery of biologically relevant compounds inspired by plant secondary metabolites, which contributes to the development of many chemotherapeutic drugs used in cancer treatment. Psidium guajava leaves present a diverse phytochemical composition including flavonoids, phenolics, meroterpenoids, and triterpenes as the major bioactive constituents. Guajadial, a caryophyllene-based meroterpenoid, has been studied for potential anticancer effects tested in tumor cells and animal experimental models. Moreover, guajadial has been reported to have a mechanism of action similar to tamoxifen, suggesting this compound as a promisor phytoestrogen-based therapeutic agent. Herein, the anti-estrogenic action and anti-proliferative activity of guajadial is reported. The enriched guajadial fraction was obtained by sequential chromatographic techniques from the crude P. guajava dichloromethane extract showing promising anti-proliferative activity in vitro with selectivity for human breast cancer cell lines MCF-7 and MCF-7 BUS (Total Growth Inhibition = 5.59 and 2.27 µg·mL-1, respectively). Furthermore, evaluation of anti-estrogenic activity in vivo was performed demonstrating that guajadial enriched fraction inhibited the proliferative effect of estradiol on the uterus of pre-pubescent rats. These results suggest a relationship between anti-proliferative and anti-estrogenic activity of guajadial, which possibly acts in tumor inhibition through estrogen receptors due to the compounds structural similarity to tamoxifen.
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Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Antagonistas de Estrogênios/farmacologia , Extratos Vegetais/química , Folhas de Planta/química , Psidium/química , Terpenos/farmacologia , Animais , Antineoplásicos/uso terapêutico , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Ovário/efeitos dos fármacos , Ratos , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Sesquiterpenos/uso terapêutico , Sesquiterpenos/toxicidade , Terpenos/química , Terpenos/uso terapêutico , Terpenos/toxicidade , Útero/efeitos dos fármacos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The anti-proliferative potential of Passiflora mollissima seeds, an underexplored agri-food waste, was investigated in this work by evaluating the molecular changes induced at transcript and metabolite expression levels on HT-29 human colon cancer cells. For this purpose, a pressurized-liquid extract from P. mollissima seeds obtained under optimized conditions was used for the treatment of HT-29 cells and a multi-omics strategy applied, integrating transcriptomics and metabolomics analysis, along with viability and cell cycle assays to study the molecular mechanisms that explain the anti-proliferative activity of this fruit by-product. After treatment for 48 and 72 h, the viability of HT-29 colon cancer cells was markedly affected, whereas minor effects were observed on normal human colon fibroblast cells. The bioactive extract was shown to arrest HT-29 cells in the S and G2/M phases of the cell cycle, which might be mediated by the inactivation of the FAT10 cancer signalling pathway among other genes identified as altered in the transcriptomic analysis. In addition, cellular redox homeostasis, as well as the polyamines pathway and methionine metabolism were found to be affected as suggested from the metabolomics data. Finally, the Foodomics integration enabled the identification of genes, such as MAD2L1, involved in the polyamine and glutathione metabolism, or the inactivation of the NUPR1 transcription factor, that might be related with the alteration of the intracellular ceramide levels in response to endoplasmic reticulum stress.
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Antineoplásicos Fitogênicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Passiflora/química , Extratos Vegetais/farmacologia , Sementes/química , Antineoplásicos Fitogênicos/química , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Glutationa/metabolismo , Humanos , Metabolômica , Metionina/metabolismo , Extratos Vegetais/química , Poliaminas/metabolismoRESUMO
Quaternary or spirocyclic 3-substituted-3-hydroxy-2-oxindole is considered a privileged scaffold. In other words, it is a molecular core present on several compounds with a wide spectrum of biological activities. Among its precursors, activated ketones (isatin nucleus) can be used as interesting starting points to Morita-Baylis-Hillman adducts derivatives, a class of compounds with good cytotoxic potential. In this paper, we present the synthesis, anti-proliferative activity against lung cancer cell line and a theoretical conformational study of 21 of Morita-Baylis-Hillman adducts from isatin derivatives, by DFT quantum chemical calculations, followed by a SAR and QSAR analysis. Besides, an efficient synthetic protocol and good biological activity profile were highlighted interesting observations about 1H NMR experimental spectra, molecular modeling results and crystallographic data available.
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Antineoplásicos/química , Antineoplásicos/farmacologia , Técnicas de Química Sintética , Isatina/química , Isatina/farmacologia , Modelos Teóricos , Espectroscopia de Prótons por Ressonância Magnética , Antineoplásicos/síntese química , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Humanos , Concentração Inibidora 50 , Isatina/análogos & derivados , Isatina/síntese química , Modelos Moleculares , Estrutura Molecular , Relação Quantitativa Estrutura-AtividadeRESUMO
ABSTRACT At present, there is a rapidly growing interest in studying the cytotoxic effects of Artemisia herba alba Asso, Asteraceae, in various cancer cell lines. However, its antitumor effectiveness has not been investigated. Therefore, the current study was conducted to study the effect of A. herba alba extract on the proliferation and growth of solid tumor cells in Ehrlich Solid Carcinoma bearing mice. Oral administration of A. herba alba extract resulted in significant reductions in tumor size, tumor weight and mice body weight, as well as caused concurrent significant increases in the DNA breakages and apoptotic DNA damage induction in a time-dependent manner. A. herba alba extract also raised the expression level of p53 gene and reduced of K-ras expression in a time-dependent manner. Minor histological lesions were observed in the liver and kidney tissues sections of mice administered A. herba alba extract compared with the high histological lesions observed in the liver and kidney tissues of artesunate and cisplatin treated groups. Thus, we concluded that A. herba alba extract exhibited promising potential antitumor efficacy with greater safety than artesunate and the commercially used anticancer drug cisplatin in mice.
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The skin is the largest organ of the human body and its main function is to protect it from the external environment. It is exposed to injuries that require a rapid healing process to recover its functionality. Microorganisms inhabit the skin, which makes up the normal microbial flora, but in situations of injury they can cause infections that slow down the regeneration process. Therefore, there is a great interest in the development of alternative methods to accelerate the regeneration process and prevent infections. In this work, the efficacy of flavonoid 3-O-methylgalangine and the terpenic derivative Filifolinone and its mixtures, isolated from plants of the genus Heliotropium, on the stimulation of cell proliferation was evaluated. The results showed that the mixtures stimulated proliferation and migration in MA104 cells mainly due to the presence of Filifolinone, that together with the known antibacterial activity of 3-O-methylgalangine, opens new alternatives for the use of natural compounds in healing processes.
La piel es el oÌrgano maÌs grande del cuerpo humano y su funcioÌn principal es protegerla del entorno externo. EstaÌ expuesta a lesiones que requieren un proceso de curacioÌn raÌpido para recuperar su funcionalidad. Los microorganismos que habitan en la piel, constituyen la flora microbiana normal, pero en situaciones de lesioÌn pueden causar infecciones que retardan el proceso de regeneracioÌn. Por lo tanto, existe un gran intereÌs en el desarrollo de meÌtodos alternativos para acelerar el proceso de regeneracioÌn y prevenir infecciones. En este trabajo, se evaluoÌ la eficacia del flavonoide 3-O-metilgalangina y el derivado terpeÌnico Filifolinona y sus mezclas, aisladas de plantas del geÌnero Heliotropium, en la estimulacioÌn de la proliferacioÌn celular. Los resultados mostraron que las mezclas estimularon la proliferacioÌn y la migracioÌn en las ceÌlulas MA104 debido principalmente a la presencia de Filifolinona, que junto con la actividad antibacteriana conocida de la 3-O-metilgalangina, abre nuevas alternativas para el uso de compuestos naturales en los procesos de curacioÌn.
Assuntos
Terpenos/farmacologia , Flavonoides/farmacologia , Heliotropium , Proliferação de Células/efeitos dos fármacos , Terpenos/química , Cicatrização , Flavonoides/química , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Células Epiteliais/efeitos dos fármacosRESUMO
In this work, we report on the synthesis of two new mono-alkylated tetrandrine derivatives with acridine and anthracene units, MAcT and MAnT. The compounds were fully characterized by physicochemical techniques and single-crystal X-ray diffraction analysis. In addition, both derivatives were studied as nucleotide receptors and double-stranded DNA binders in aqueous phosphate buffer at pHâ¯=â¯7.2 using UV-vis and fluorescence spectroscopy. According to the molecular recognition studies, MAcT and MAnT exhibit high affinity (Kâ¯â¼â¯105â¯M-1) and selectivity for ds-DNA, presumably in an intercalation mode. Finally, the anti-proliferative effects of the tetrandrine derivatives on different cancer cell lines were explored, revealing promising activities. Particularly, the mono-anthracene tetrandrine derivative MAnT showed an IC50 of 2.74⯵g/mL on the HeLa cervical cancer cell line, representing a value 3.3 times smaller than that obtained for unsubstituted tetrandrine. Examination of the cytotoxic effects on the HeLa cell line by inverted microscopy suggests that the cell death mechanism consists basically in apoptosis. The molecular modelling of three ds-DNA-MAcT complexes, suggested that the macrocycles may use an intercalation binding mode towards DNA. MAcT is predicted to bind into the major groove of the ds-DNA providing non-covalent interactions such as electrostatic, van der Waals and hydrophobic interactions that lead to selectivity. Overall experimental data supports the mode of action of MAnT and MAcT as cytotoxic compounds against cancer cell lines via a DNA interaction mechanism.
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Acridinas/química , Antracenos/química , Benzilisoquinolinas/química , Compostos Macrocíclicos/síntese química , Células A549 , Acridinas/síntese química , Acridinas/farmacologia , Antracenos/síntese química , Antracenos/farmacologia , Apoptose/efeitos dos fármacos , Benzilisoquinolinas/síntese química , Benzilisoquinolinas/farmacologia , Sítios de Ligação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , DNA/química , DNA/metabolismo , Células HeLa , Humanos , Interações Hidrofóbicas e Hidrofílicas , Substâncias Intercalantes/síntese química , Substâncias Intercalantes/química , Substâncias Intercalantes/farmacologia , Compostos Macrocíclicos/química , Compostos Macrocíclicos/farmacologia , Simulação de Acoplamento Molecular , Conformação de Ácido Nucleico , Eletricidade EstáticaRESUMO
Colorectal cancer (CRC) is a disease with high incidence and mortality, constituting the fourth most common cause of death from cancer worldwide. Naphthoquinones are attractive compounds due to their biological and structural properties. In this work, 36 naphthoquinone derivatives were synthesized and their activity evaluated against HT-29 cells. Overall, high to moderate anti-proliferative activity was observed in most members of the series, with 15 compounds classified as active (1.73 < IC50 < 18.11 µM). The naphtho[2,3-b]thiophene-4,9-dione analogs showed potent cytotoxicity, 8-hydroxy-2-(thiophen-2-ylcarbonyl)naphtho[2,3-b]thiophene-4,9-dione being the compound with the highest potency and selectivity. Our results suggest that the toxicity is improved in molecules with tricyclic naphtho[2,3-b]furan-4,9-dione and naphtho[2,3-b]thiophene-4,9-dione systems 2-substituted with an electron-withdrawing group. A 3D-QSAR study of comparative molecular field analysis (CoMFA) was carried out, resulting in the generation of a reliable model (r² = 0.99 and q² = 0.625). This model allowed proposing five new compounds with two-fold higher theoretical anti-proliferative activity, which would be worthwhile to synthesize and evaluate. Further investigations will be needed to determine the mechanism involved in the effect of most active compounds which are potential candidates for new anticancer agents.
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Antineoplásicos/química , Antineoplásicos/farmacologia , Naftoquinonas/química , Naftoquinonas/farmacologia , Relação Quantitativa Estrutura-Atividade , Antineoplásicos/síntese química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Técnicas de Química Sintética , Neoplasias Colorretais , Desenho de Fármacos , Humanos , Concentração Inibidora 50 , Modelos Moleculares , Conformação Molecular , Estrutura Molecular , Naftoquinonas/síntese químicaRESUMO
BACKGROUND: Thevetia peruviana (Pers.) K. Schum or Cascabela peruviana (L.) Lippold (commonly known as ayoyote, codo de fraile, lucky nut, or yellow oleander), native to Mexico and Central America, is a medicinal plant used traditionally to cure diseases like ulcers, scabies, hemorrhoids and dissolve tumors. The purpose of this study was to evaluate the cytotoxic, antiproliferative and apoptotic activity of methanolic extract of T. peruviana fruits on human cancer cell lines. METHODS: The cytotoxic activity of T. peruviana methanolic extract was carried out on human breast, colorectal, prostate and lung cancer cell lines and non-tumorigenic control cells (fibroblast and Vero), using the MTT assay. For proliferation and motility, clonogenic and wound-healing assays were performed. Morphological alterations were monitored by trypan blue exclusion, as well as DNA fragmentation and AO/EB double staining was performed to evaluate apoptosis. The extract was separated using flash chromatography, and the resulting fractions were evaluated on colorectal cancer cells for their cytotoxic activity. The active fractions were further analyzed through mass spectrometry. RESULTS: The T. peruviana methanolic extract exhibited cytotoxic activity on four human cancer cell lines: prostate, breast, colorectal and lung, with values of IC50 1.91 ± 0.76, 5.78 ± 2.12, 6.30 ± 4.45 and 12.04 ± 3.43 µg/mL, respectively. The extract caused a significant reduction of cell motility and colony formation on all evaluated cancer cell lines. In addition, morphological examination displayed cell size reduction, membrane blebbing and detachment of cells, compared to non-treated cancer cell lines. The T. peruviana extract induced apoptotic cell death, which was confirmed by DNA fragmentation and AO/EB double staining. Fractions 4 and 5 showed the most effective cytotoxic activity and their MS analysis revealed the presence of the secondary metabolites: thevetiaflavone and cardiac glycosides. CONCLUSION: T. peruviana extract has potential as natural anti-cancer product with critical effects in the proliferation, motility, and adhesion of human breast and colorectal cancer cells, and apoptosis induction in human prostate and lung cancer cell lines, with minimal effects on non-tumorigenic cell lines.
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Antineoplásicos Fitogênicos/uso terapêutico , Glicosídeos Cardíacos/uso terapêutico , Flavonas/uso terapêutico , Neoplasias/tratamento farmacológico , Fitoterapia , Extratos Vegetais/uso terapêutico , Thevetia/química , Animais , Antineoplásicos Fitogênicos/farmacologia , Apoptose , Neoplasias da Mama/tratamento farmacológico , Glicosídeos Cardíacos/análise , Glicosídeos Cardíacos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Colorretais/tratamento farmacológico , Fragmentação do DNA , Feminino , Flavonas/análise , Flavonas/farmacologia , Frutas , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , México , Extratos Vegetais/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Células VeroRESUMO
Cicatrization can be divided into three phases: inflammation, fibroblastic, maturation and remodeling [1]. The extracellular matrix may be replaced by a stronger and more elastic connective tissue. In a scar collagen is the major component of the mature connective tissue [2]. In homeopathic area, the greater is the investigated segment ultra dilutions [6]. However, little research has been done to explore the effect of dynamized drugs in in vitro cell culture [4]. Using the Zincum metallicum 6CH and Calendula officinalis 6CH applied independently in different concentrations in fibroblast cultures sought to determine the increase in proliferative activity using techniques such as IC50, MTT, flow cytometry and quantification of collagen. As expected from the literature, ie both homeopathic according to the literature are used for treatments that Require skin healing, both showed increased proliferative activity, having Calendula most cellular response, presenting as cell cycle stimulating checked via flow cytometry.(AU)
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Humanos , Cicatrização , Zincum Metallicum/uso terapêutico , /uso terapêutico , Altas Potências , FibroblastosRESUMO
Cicatrization can be divided into three phases: inflammation, fibroblastic, maturation and remodeling [1]. The extracellular matrix may be replaced by a stronger and more elastic connective tissue. In a scar collagen is the major component of the mature connective tissue [2]. In homeopathic area, the greater is the investigated segment ultra dilutions [6]. However, little research has been done to explore the effect of dynamized drugs in in vitro cell culture [4]. Using the Zincum metallicum 6CH and Calendula officinalis 6CH applied independently in different concentrations in fibroblast cultures sought to determine the increase in proliferative activity using techniques such as IC50, MTT, flow cytometry and quantification of collagen. As expected from the literature, ie both homeopathic according to the literature are used for treatments that Require skin healing, both showed increased proliferative activity, having Calendula most cellular response, presenting as cell cycle stimulating checked via flow cytometry.
Assuntos
Humanos , Cicatrização , Zincum Metallicum/uso terapêutico , /uso terapêutico , Altas Potências , FibroblastosRESUMO
AIMS: Anti-neoplastic activity induced by cannabinoids has been extensively documented for a number of cancer cell types; however, this topic has been explored in gastric cancer cells only in a limited number of approaches. Thus, the need of integrative and comparative studies still persists. MATERIALS AND METHODS: In this study we tested and compared the effects of three different cannabinoid receptor agonists-anandamide (AEA), (R)-(+)-methanandamide (Meth-AEA) and CP 55,940 (CP)- on gastric cancer cell morphology, viability and death events in order to provide new insights to the use of these agents for therapeutic purposes. KEY FINDINGS: The three agents tested exhibited similar concentration-dependent effects in the induction of changes in cell morphology and cell loss, as well as in the decrease of cell viability and DNA laddering in the human gastric adenocarcinoma cell line (AGS). Differences among the cannabinoids tested were mostly observed in the density of cells found in early and late apoptosis and necrosis, favoring AEA and CP as the more effective inducers of apoptotic mechanisms, and Meth-AEA as a more effective inducer of necrosis through transient and rapid apoptosis. SIGNIFICANCE: Through a comparative approach, our results support and confirm the therapeutic potential that cannabinoid receptor agonists exert in gastric cancer cells and open possibilities to use cannabinoids as part of a new gastric cancer therapy.
Assuntos
Agonistas de Receptores de Canabinoides/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Gástricas/patologia , Linhagem Celular Tumoral , Citometria de Fluxo , HumanosRESUMO
In the search for novel chemotherapeutic agents for cancer treatment, capsaicin has been shown to inhibit proliferation and induce apoptosis in various types of cancer cell line, including leukaemia cell lines. The capsaicin analogues, rinvanil and phenylacetylrinvanil (PhAR), share a binding affinity for vanilloid receptors and may have biological activities similar to capsaicin; however, their anticancer potential has not yet been reported. This study analyses the antineoplastic activities of rinvanil and PhAR in leukaemia versus normal cells. P388, J774 and WEHI-3 leukaemia cell lines, as well as mouse bone marrow mononuclear cells, were cultured with varying concentrations of rinvanil and PhAR. Following this, proliferation and apoptosis were determined by the sulforhodamine B (SRB) assay and DNA ladder. Cultured leukaemia cell lines and mouse bone marrow mononuclear cells demonstrated a dose-dependent inhibition of proliferation, while non-diseased cells were less sensitive to the cytotoxic effect of capsaicin, rinvanil and PhAR. Rinvanil and PhAR also induced apoptosis in leukaemia cell lines but not in bone marrow. Given the lower IC50 values for apoptosis induction in leukaemia cells compared with that of normal cells, PhAR is a promising selective anticancer agent.
RESUMO
Os peptideos INKKI e YPQPFTE foram isolados a patir da hidrolise da B caseina bovina e correspondem as sequencias 26-30 e 114-121 respectivamente. Trabalhos anteriores mostram que estes peptideos apresentaram atividades potenciadoras da bradicinina ...
Peptides INKKI and YPQPFTE were isolated from the bovine B casein after this hidrolysis corresponding to the 23-30 and 114-121 sequence respectively. Previous works had shown that these peptides presented bradkynin potentialing activity ...