Evaluation of Cytotoxic effect of Moringa peregrina seeds on Oral Cancer, CAL 27, Cell Line and Red Blood Cells Hemolysis / Evaluación del efecto citotóxico de las semillas de Moringa peregrina en el cáncer oral, CAL 27, líneas celulares y hemólisis de glóbulos rojos

Background: Moringa peregrina Forssk is a well-known plant in ethnomedicine due to its widespread uses in various diseases like cough, wound healing, rhinitis, fever, and detoxification. The plant seeds contain compounds that are cytotoxic to many cancer cells. During the therapeutic use of plants via the oral route, some compounds present in the plants may be cytotoxic to normal cell lines and red blood cells. Objective: This study was the first report of investigation of the cytotoxic profile on oral cancer, CAL 27, cell line, and hemolytic activities on human erythrocytes of Moringa peregrina seeds ethanolic extract (MPSE). Methods: MPSE was screened for its cytotoxic effect against oral cancer, CAL 27, cell line using 3-(4, 5-dimethylthiazol-2-yl)-2, 5,-diphenyltetrazolium bromide (MTT) assay. The toxicity of MPSE on human erythrocytes was determined by in vitro hemolytic assay. Results: MPSE showed significant anti-proliferative activity against oral cancer, CAL 27 cell line at lower concentrations with half maximal inhibitory concentration (IC50) value of 21.03 µg/mL. At 1,000 µg/ml of MPSE, the maximum hemolysis was found to be 14.3% which is within safer limit. Conclusions: This study revealed a potential anti-oral cancer of MPSE and provided a baseline for its potential use in oral cancer treatment with minimum hemolytic effect on human RBCs.

La Moringa peregrina Forssk es una planta muy conocida en etnomedicina debido a sus usos generalizados en diversas enfermedades como la tos, la cicatrización de heridas, la rinitis, la fiebre y la desintoxicación. Las semillas de la planta contienen compuestos citotóxicos para muchas células cancerosas. Durante el uso terapéutico de las plantas por vía oral, algunos compuestos presentes en ellas pueden ser citotóxicos para las líneas celulares normales y los glóbulos rojos. Objetivo: Este estudio fue el primer informe de investigación del perfil citotóxico sobre el cáncer oral, CAL 27, línea celular, y las actividades hemolíticas en eritrocitos humanos del extracto etanólico de semillas de Moringa peregrina (MPSE). Métodos: Se examinó el efecto citotóxico del MPSE contra la línea celular de cáncer oral CAL 27 mediante el ensayo con bromuro de 3-(4, 5-dimetiltiazol-2-il)-2, 5,-difeniltetrazolio (MTT). La toxicidad del MPSE sobre los eritrocitos humanos se determinó mediante un ensayo hemolítico in vitro. Resultados: MPSE mostró una actividad antiproliferativa significativa contra el cáncer oral, línea celular CAL 27 a concentraciones más bajas con un valor de concentración inhibitoria media máxima (IC50) de 21,03 µg/mL. A 1.000 µg/ml de MPSE, la hemólisis máxima fue del 14,3%, lo que está dentro del límite de seguridad. Conclusiones: Este estudio reveló un potencial anticancerígeno oral de MPSE y proporcionó una base para su uso potencial en el tratamiento del cáncer oral con un efecto hemolítico mínimo en los glóbulos rojos humanos.

Cytotoxic, phytotoxic and insecticidal potential of Achillea millefolium L. and Chaerophyllum villosum wall. ex dc / Potencial citotóxico, fitotóxico e insecticida de Achillea millefolium L. e Chaerophyllum villosum

The methanolic, chloroformic and aqueous extract of Achillea millefolium and Chaerophyllum villosum were investigated for cytotoxicity, phytotoxic and insecticidal activities. Cytotoxicity was investigated by brine shrimp lethality assay indicating that the crude methanolic extract of A.millefolium and chloroformic extract of C.villosum revealed highest mortality of brine shrimps with (LD50 of 52.60 µg/ml) and (14.81 µg/ml). Phytotoxicity was evaluated using the Lemna minor bioassay which revealed that the crude methanolic extract of A.millefolium and C.villosum extract has maximum inhibition of Lemna minor with (Fl50 6.60 µg/ml) and (0.67 µg/ml).The insecticidal activity showed that among all the insects studied it was observed that methanolic extract of A. millefoliumand C. villosum was highly toxic to Sphenoptera dadkhani with (LD50=4.17 µg/ml) and (0.34 µg/ml). From the present study it can be concluded that different extracts from A. millefolium and C. villosum showed good cytotoxic, phytotoxic and insecticidal activity in a dose dependent manner.

Neste estudo, os extratos metanólico, clorofórmico e aquoso de Achillea millefolium e Chaerophyllum villosum foram analisados em relação à citotoxicidade, atividade fitotóxica e inseticida. A citotoxicidade foi analisada através do ensaio de letalidade de artémia, indicando que o extrato metanólico bruto de A. millefolium e o extrato clorofórmico de C. villosum revelaram maior mortalidade de artêmias com DL50 de 52,60 µg/ml e 14,81 µg/ml. A fitotoxicidade foi avaliada utilizando o bioensaio de Lemna minor que revelou que o extrato metanólico bruto de A. millefolium e extrato de C. villosum têm inibição máxima de Lemna minor com Fl50 6,60 µg/ml e 0,67 µg/ml. A atividade inseticida mostrou que dentre todos os insetos estudados, o extrato metanólico de A. millefolium e de C. villosum foi altamente tóxico para Sphenoptera dadkhanicom DL50 = 4,17 µg/ml e 0,34 µg/ml . Por outro lado, diferentes extratos, como A. millefolium e C. villosum apresentaram boa atividade citotóxica, fitotóxica e inseticida de forma dose-dependente.

Cytotoxic effects of crotoxin from Crotalus durissus terrificus snake in canine mammary tumor cell lines

Background: Mammary gland tumors are the most prevalent neoplasm in intact female dogs, and they are good natural models to study comparative oncology. Most canine mammary malignancies, as in women, are commonly refractory to conventional therapies and demand continuous new therapeutic approaches. Crotalus durissus terrificus, also called rattlesnake, has more than 60 different proteins in its venom with multiple pharmaceutical uses, such as antitumor, antiviral, and antimicrobial action. Crotoxin, a potent β-neurotoxin formed by the junction of two subunits, a basic subunit (CB-PLA2) and an acidic subunit (crotapotin), has already been reported to have anticancer properties in different types of cancers. Methods: In this work, we describe the cytotoxic potential of crotoxin and its subunits compared to doxorubicin (drug of choice) in two canine mammary carcinoma cell lines. Results: Crotoxin, CB-PLA2, crotalic venom, and doxorubicin decreased cell viability and the ability to migrate in a dose-dependent manner, and crotapotin did not present an antitumoral effect. For all compounds, the predominant cell death mechanism was apoptosis. In addition, crotoxin did not show toxicity in normal canine mammary gland cells. Conclusion: Therefore, this work showed that crotoxin and CB-PLA2 had cytotoxic activity, migration inhibition, and pro-apoptotic potential in canine mammary gland carcinoma cell lines, making their possible use in cancer research.

Selective cytotoxic effect of Annona muricata L. in HCC1954 (HER2+) breast cancer cells / Efecto citotóxico selectivo de Annona muricata L. en células HCC1954 (HER2+) de cáncer de mama

Annona muricata Linn. (Annonaceae) is a tropical plant with multiple beneficial health effects including anticancer properties. In breast cancer patients, overexpression of the HER2 oncoprotein corresponds to a poor prognosis, thus the main purpose of this study was to evaluate the cytotoxicity of ethanolic extracts from dried and fresh leaf of A. muricata on HER2+ breast cancer cells. MTT assays were performed and IC50 determined in HCC1954 (HER2+) cells, as well as in MCF7 (HER-) and peripheral blood mononuclear cells (PBMC) used as controls. Total polyphenol content evaluation and phytochemical screening were also performed. The cytotoxic effect of A. muricata extracts (125-1000 µg/mL) was dose-dependent and cell-type specific. The extracts exhibited higher cytotoxicity against HCC1954 than MCF7 cells, but weak toxicity against PBMC. This is the first report of the cytotoxic effect of A. muricata on HCC1954 cells, highlighting its potential for treating anti-estrogen-resistant breast cancers and low toxicity against PBMC.

Annona muricata Linn. (Annonaceae) es una planta tropical con múltiples efectos benéficos en la salud incluyendo propiedades antitumorales. En pacientes con cáncer de mama la sobreexpresión del oncogen HER2 corresponde a un mal pronóstico, por lo que el objetivo principal de este estudio fue evaluar la citotoxicidad de extractos etanólicos de hojas secas y frescas de A. muricata en células tumorales de mama HER2+. Se aplicaron pruebas de MTT y se determinaron IC50en células HCC1954 (HER2+); se utilizaron células MCF7 (HER-) y células mononucleares de sangre periférica (PBMC) como control. Se valoró también el contenido en polifenoles totales, y se realizó un tamizaje fitoquímico. El efecto citotóxico de los extractos de A. muricata (125-1000 µg/mL) fue dosis-dependiente y específico para cada tipo celular. Los extractos presentaron mayor actividad citotóxica contra HCC1954 en comparación con MCF7 y baja toxicidad contra PBMC. Este es el primer reporte del efecto citotóxico de A. muricata en HCC1954 y destaca su potencial terapéutico para tratamiento de cáncer de mama resistentes a antiestrógeno y baja citotoxicidad contra PBMC.

Transcriptional Activation of a Pro-Inflammatory Response (NF-κB, AP-1, IL-1ß) by the Vibrio cholerae Cytotoxin (VCC) Monomer through the MAPK Signaling Pathway in the THP-1 Human Macrophage Cell Line.

This study describes, to some extent, the VCC contribution as an early stimulation of the macrophage lineage. Regarding the onset of the innate immune response caused by infection, the ß form of IL-1 is the most important interleukin involved in the onset of the inflammatory innate response. Activated macrophages treated in vitro with VCC induced the activation of the MAPK signaling pathway in a one-hour period, with the activation of transcriptional regulators for a surviving and pro-inflammatory response, suggesting an explanation inspired and supported by the inflammasome physiology. The mechanism of IL-1ß production induced by VCC has been gracefully outlined in murine models, using bacterial knockdown mutants and purified molecules; nevertheless, the knowledge of this mechanism in the human immune system is still under study. This work shows the soluble form of 65 kDa of the Vibrio cholerae cytotoxin (also known as hemolysin), as it is secreted by the bacteria, inducing the production of IL-1ß in the human macrophage cell line THP-1. The mechanism involves triggering the early activation of the signaling pathway MAPKs pERK and p38, with the subsequent activation of (p50) NF-κB and AP-1 (cJun and cFos), determined by real-time quantitation. The evidence shown here supports that the monomeric soluble form of the VCC in the macrophage acts as a modulator of the innate immune response, which is consistent with the assembly of the NLRP3 inflammasome actively releasing IL-1ß.

Naphth[1,2-d]imidazoles Bioactive from ß-Lapachone: Fluorescent Probes and Cytotoxic Agents to Cancer Cells.

Theranostics combines therapeutic and imaging diagnostic techniques that are extremely dependent on the action of imaging agent, transporter of therapeutic molecules, and specific target ligand, in which fluorescent probes can act as diagnostic agents. In particular, naphthoimidazoles are potential bioactive heterocycle compounds to be used in several biomedical applications. With this aim, a group of seven naphth[1,2-d]imidazole compounds were synthesized from ß-lapachone. Their optical properties and their cytotoxic activity against cancer cells and their compounds were evaluated and confirmed promising values for molar absorptivity coefficients (on the order of 103 to 104), intense fluorescence emissions in the blue region, and large Stokes shifts (20-103 nm). Furthermore, the probes were also selective for analyzed cancer cells (leukemic cells (HL-60). The naphth[1,2-d]imidazoles showed IC50 between 8.71 and 29.92 µM against HL-60 cells. For HCT-116 cells, values for IC50 between 21.12 and 62.11 µM were observed. The selective cytotoxicity towards cancer cells and the fluorescence of the synthesized naphth[1,2-d]imidazoles are promising responses that make possible the application of these components in antitumor theranostic systems.

Cytotoxicity of capsaicin and its analogs in vitro / Citotoxicidade da capsaicina e seus análogos in vitro

Capsaicin (CAP) is the main compound responsible for the spicy flavor of Capsicum plants. However, its application can be inhibited due to its pungency and toxicity. This study aimed to evaluate and compare the cytotoxic effect of CAP and its analogs N-benzylbutanamide (AN1), N-(3-methoxybenzyl) butanamide (AN2), N-(4-hydroxy-3-methoxybenzyl) butanamide (AN3), N-(4-hydroxy-3-methoxybenzyl) hexanamide (AN4) and N-(4-hydroxy-3-methoxybenzyl) tetradecanamide (AN5) on the hepatoma cells of Rattus norvegicus using the MTT test. The results showed cytotoxicity of CAP at concentrations of 100, 150, 175, and 200 µM (24 hours), AN1 at 150 and 175 µM (48 hours), AN2 at 50 µM (24 hours) and 10, 25, 50, and 75 µM (48 hours), AN4 at 175 µM (24 hours), and AN5 at 50 µM (48 hours). Removing the hydroxyl radical from the vanillyl group of capsaicin, together with reducing the acyl chain to 3 carbons, which is the case of AN2, resulted in the best biological activity. Increasing the carbon chain in the acyl group of the capsaicin molecule, which is the case of AN5, also showed evident cytotoxic effects. The present study proves that the chemical modifications of capsaicin changed its biological activity.

A capsaicina (CAP) é o principal composto responsável pelo sabor picante das plantas de Capsicum. No entanto sua aplicação pode ser inibida devido à sua pungência e toxicidade. O objetivo do presente estudo foi avaliar e comparar o efeito citotóxico do CAP e seus análogos N-benzilbutanamida (AN1), N-(3-metoxibenzil)butanamida (AN2), N -(4-hidroxi-3-metoxibenzil)butanamida (AN3), N-(4-hidroxi-3-metoxibenzil) hexanamida (AN4) e N-(4-hidroxi-3-metoxibenzil) tetradecanamida (AN5) em células do hepatoma de Rattus norvegicus pelo teste do MTT. Os resultados mostraram citotoxicidade da CAP em concentrações de 100, 150, 175 e 200 µM (24 horas), AN1 em 150 e 175 µM (48 horas), AN2 em 50 µM (24 horas) e 10, 25, 50 e 75 µM (48 horas), AN4 em 175 µM (24 horas) e AN5 em 50 µM (48 horas). A remoção do radical hidroxila do grupo vanilil da capsaicina, juntamente com a redução da cadeia acila para 3 carbonos, caso do AN2, foi o que resultou na melhor atividade biológica. O aumento da cadeia carbônica no grupo acil da molécula de capsaicina, caso da AN5, também demonstrou efeitos citotóxicos evidentes. O presente estudo comprova que as modificações químicas da capsaicina alteraram sua atividade biológica.

Bioactive properties of Persea lingue Ness (Lauraceae) fruit and leaf extracts / Propriedades bioativas de extratos de folhas e frutos de Persea lingue Ness (Lauraceae)

Persea lingue Ness is a tree species that lives mainly in temperate forests of south-central Chile. Its leaves are used in ethnomedicine, the fruit is a drupe similar to that of the avocado and has not been studied. The aim of this study was to determine the cytotoxicity in leukemia cell and antibacterial activity, along with some chemical content characteristics of P. lingue fruit and leaf extracts. The antibacterial activity was determined by the inhibition of bacterial growth in liquid medium assay against Gram-positive and Gram-negative bacteria. The leukemia cell lines Kasumi-1 and Jurkat were used to evaluate the cytotoxic activity by using propidium iodide and AlamarBlue assays. Total phenolic, flavonoid, condensed tannin, alkaloid and lipid contents were evaluated in the fruit and in the leaf extracts. The antioxidant activity of both extracts were also elavaluated. Leaf extract presented the highest content of total phenols, condensed tannins and flavonoids, and also the highest antioxidant activity. While the fruit extract has a higher amount of lipids and alkaloids and the high antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus megaterium and Micrococcus luteus. The leaf extract only showed activity against M. luteus. Concerning the cytotoxic activity, only the fruit extract showed cytotoxicity against the cell lines Jurkat and Kasumi-1. P. lingue fruit extract is a potential source of biologically active molecules for the development of new drugs to be used in some types of leukemia, as well as antibacterial agent.(AU)

Persea lingue Ness é uma árvore que vive principalmente na floresta temperada do centro-sul do Chile. As folhas são usadas na etnomedicina. O fruto é uma drupa similar ao abacate e que nunca foi pesquisada anteriormente. O objetivo deste estudo foi o de avaliar a citotoxicidade em células leucêmicas e as atividades antibacterianas, assim como algumas características químicas do extrato de fruto e da folha do P. lingue. As atividades antibacterianas foram determinadas pelo método da inibição do crescimento bacteriano em meio líquido empregando-se bactérias Gram-positivas e Gram-negativas. As linhagens celulares leucêmicas, Kasumi-1 e Jurkat foram usadas para avaliar a atividade citotóxica em ensaios empregando-se iodeto de propídio e AlamarBlue. Foram avaliados os teores totais de fenóis, flavonóides, taninos condensados, alcalóides e lipídeos presentes nos extratos das folhas e dos frutos. As atividades antioxidantes de ambos os extratos também foram avaliadas. O extrato das folhas foi o que apresentou o maior conteúdo de fenóis, taninos condensados e flavonóides totais e a maior atividade antioxidante. Já o extrato de fruto apresentou a maior quantidade de lipídios e alcaloides e a melhor atividade antibacteriana contra Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus megaterium e Micrococcus luteus. Já o extrato das folhas apresentou apenas atividade contra M. luteus. Em relação à atividade citotóxica, apenas o extrato do fruto apresentou citotoxicidade contra as linhagens celulares Jurkat e Kasumi-1. Em resumo, o extrato do fruto de P. lingue é uma potencial fonte de moléculas com atividade biológica para o desenvolvimento de novos fármacos a serem utilizados em alguns tipos de leucemia, bem como agente antibacteriano.(AU)

Bioactive properties of Persea lingue Ness (Lauraceae) fruit and leaf extracts / Propriedades bioativas de extratos de folhas e frutos de Persea lingue Ness (Lauraceae)

Persea lingue Ness is a tree species that lives mainly in temperate forests of south-central Chile. Its leaves are used in ethnomedicine, the fruit is a drupe similar to that of the avocado and has not been studied. The aim of this study was to determine the cytotoxicity in leukemia cell and antibacterial activity, along with some chemical content characteristics of P. lingue fruit and leaf extracts. The antibacterial activity was determined by the inhibition of bacterial growth in liquid medium assay against Gram-positive and Gram-negative bacteria. The leukemia cell lines Kasumi-1 and Jurkat were used to evaluate the cytotoxic activity by using propidium iodide and AlamarBlue assays. Total phenolic, flavonoid, condensed tannin, alkaloid and lipid contents were evaluated in the fruit and in the leaf extracts. The antioxidant activity of both extracts were also elavaluated. Leaf extract presented the highest content of total phenols, condensed tannins and flavonoids, and also the highest antioxidant activity. While the fruit extract has a higher amount of lipids and alkaloids and the high antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus megaterium and Micrococcus luteus. The leaf extract only showed activity against M. luteus. Concerning the cytotoxic activity, only the fruit extract showed cytotoxicity against the cell lines Jurkat and Kasumi-1. P. lingue fruit extract is a potential source of biologically active molecules for the development of new drugs to be used in some types of leukemia, as well as antibacterial agent.

Persea lingue Ness é uma árvore que vive principalmente na floresta temperada do centro-sul do Chile. As folhas são usadas na etnomedicina. O fruto é uma drupa similar ao abacate e que nunca foi pesquisada anteriormente. O objetivo deste estudo foi o de avaliar a citotoxicidade em células leucêmicas e as atividades antibacterianas, assim como algumas características químicas do extrato de fruto e da folha do P. lingue. As atividades antibacterianas foram determinadas pelo método da inibição do crescimento bacteriano em meio líquido empregando-se bactérias Gram-positivas e Gram-negativas. As linhagens celulares leucêmicas, Kasumi-1 e Jurkat foram usadas para avaliar a atividade citotóxica em ensaios empregando-se iodeto de propídio e AlamarBlue. Foram avaliados os teores totais de fenóis, flavonóides, taninos condensados, alcalóides e lipídeos presentes nos extratos das folhas e dos frutos. As atividades antioxidantes de ambos os extratos também foram avaliadas. O extrato das folhas foi o que apresentou o maior conteúdo de fenóis, taninos condensados e flavonóides totais e a maior atividade antioxidante. Já o extrato de fruto apresentou a maior quantidade de lipídios e alcaloides e a melhor atividade antibacteriana contra Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus megaterium e Micrococcus luteus. Já o extrato das folhas apresentou apenas atividade contra M. luteus. Em relação à atividade citotóxica, apenas o extrato do fruto apresentou citotoxicidade contra as linhagens celulares Jurkat e Kasumi-1. Em resumo, o extrato do fruto de P. lingue é uma potencial fonte de moléculas com atividade biológica para o desenvolvimento de novos fármacos a serem utilizados em alguns tipos de leucemia, bem como agente antibacteriano.

Long-term resistance to 5-fluorouracil promotes epithelial-mesenchymal transition, apoptosis evasion, autophagy, and reduced proliferation rate in colon cancer cells.

The drug, 5-fluorouracil (5FU) is a standard first-line treatment for colorectal cancer (CRC) patients. However, drug resistance acquisition remains an important challenge for effective clinical outcomes. Here, we established a long-term drug-resistant CRC model and explored the cellular events underlying 5FU resistance. We showed that 5FU-treated cells (HCT-116 5FUR) using a prolonged treatment protocol were significantly more resistant than parental cells. Likewise, cell viability and IC50 values were also observed to increase in HCT-116 5FUR cells when treated with increasing doses of oxaliplatin, indicating a cross-resistance mechanism to other cytotoxic agents. Moreover, HCT-116 5FUR cells exhibited metabolic and molecular changes, as evidenced by increased thymidylate synthase levels and upregulated mRNA levels of ABCB1. HCT-116 5FUR cells were able to overcome S phase arrest and evade apoptosis, as well as activate autophagy, as indicated by increased LC3B levels. Cells treated with low and high doses displayed epithelial-mesenchymal transition (EMT) features, as observed by decreased E-cadherin and claudin-3 levels, increased vimentin protein levels, and increased SLUG, ZEB2 and TWIST1 mRNA levels. Furthermore, HCT-116 5FUR cells displayed enhanced migration and invasion capabilities. Interestingly, we found that the 5FU drug-resistance gene signature is positively associated with the mesenchymal signature in CRC samples, and that ABCB1 and ZEB2 co-expressed at high levels could predict poor outcomes in CRC patients. Overall, the 5FU long-term drug-resistance model established here induced various cellular events, and highlighted the importance of further efforts to identify promising targets involved in more than one cellular event to successfully overcome drug-resistance.

Solid Tumors and Kinase Inhibition: Management and Therapy Efficacy Evolution.

The increasing numbers of cancer cases worldwide and the exceedingly high mortality rates of some tumor subtypes raise the question about if the current protocols for cancer management are effective and what has been done to improve upon oncologic patients' prognoses. The traditional chemo-immunotherapy options for cancer treatment focus on the use of cytotoxic agents that are able to overcome neoplastic clones' survival mechanisms and induce apoptosis, as well as on the ability to capacitate the host's immune system to hinder the continuous growth of malignant cells. The need to avert the highly toxic profiles of conventional chemo-immunotherapy and to overcome the emerging cases of tumor multidrug resistance has fueled a growing interest in the field of precision medicine and targeted molecular therapies in the last couple of decades, although relatively new alternatives in oncologic practices, the increased specificity, and the positive clinical outcomes achieved through targeted molecular therapies have already consolidated them as promising prospects for the future of cancer management. In recent years, the development and application of targeted drugs as tyrosine kinase inhibitors have enabled cancer treatment to enter the era of specificity. In addition, the combined use of targeted therapy, immunotherapy, and traditional chemotherapy has innovated the standard treatment for many malignancies, bringing new light to patients with recurrent tumors. This article comprises a series of clinical trials that, in the past 5 years, utilized kinase inhibitors (KIs) as a monotherapy or in combination with other cytotoxic agents to treat patients afflicted with solid tumors. The results, with varying degrees of efficacy, are reported.

Evaluation of the cytotoxic and mutagenic potential of Rosmarinus officinalis L. essential oil through the Allium cepa Leach bioassay

The species Rosmarinus officinalisL. (rosemary) is an herb from the Lamiaceae family, widely used in cooking as a food preservative, seasoning or condiment. It also stands out for its therapeutic properties, mainly presenting antioxidant, antibacterial and antitumor activity. The aim of this study was to evaluate the cytotoxic and mutagenic activity of R. officinalis L. essential oil through the Allium cepabioassay. This test constitutes an excellent plant model routinely used due to its sensitivity, low cost and good correlation with test systems in mammals. The defined concentrations for carrying out the test were 750, 243, 81 and 27 µg mL-1. Five bulbs were used, 4 roots of each, measuring approximately 2 cm, and they were analyzed on two slides. All assays were performed at least in triplicate and compared to the negative control. The statistical test of analysis of variance (ANOVA with a fixed factor) was used, followed by Tukey's multiple comparisons test, for p< 0.05. For this purpose, the GraphPad Prism program (version 6.0) was used. The results showed a cytotoxic and mutagenic effect for all concentrations used of the essential oil of R. officinalisL. However, it is important to conduct further research using other genotoxicological tests with different endpoints and at different concentrations, in order to clarify the interaction of the essential oil of the species R. officinalisL. with the genetic material of the cell and its possible mechanism of action.(AU)

A Ferrofluid with Surface Modified Nanoparticles for Magnetic Hyperthermia and High ROS Production.

A ferrofluid with 1,2-Benzenediol-coated iron oxide nanoparticles was synthesized and physicochemically analyzed. This colloidal system was prepared following the typical co-precipitation method, and superparamagnetic nanoparticles of 13.5 nm average diameter, 34 emu/g of magnetic saturation, and 285 K of blocking temperature were obtained. Additionally, the zeta potential showed a suitable colloidal stability for cancer therapy assays and the magneto-calorimetric trails determined a high power absorption density. In addition, the oxidative capability of the ferrofluid was corroborated by performing the Fenton reaction with methylene blue (MB) dissolved in water, where the ferrofluid was suitable for producing reactive oxygen species (ROS), and surprisingly a strong degradation of MB was also observed when it was combined with H2O2. The intracellular ROS production was qualitatively corroborated using the HT-29 human cell line, by detecting the fluorescent rise induced in 2,7-dichlorofluorescein diacetate. In other experiments, cell metabolic activity was measured, and no toxicity was observed, even with concentrations of up to 4 mg/mL of magnetic nanoparticles (MNPs). When the cells were treated with magnetic hyperthermia, 80% of cells were dead at 43 °C using 3 mg/mL of MNPs and applying a magnetic field of 530 kHz with 20 kA/m amplitude.

Structural, thermal, electronic, vibrational, magnetic, and cytotoxic properties of chloro(glycinato-N,O)(1,10-phenanthroline-N,N')­copper(II) trihydrate coordination complex.

Chloro(glycinato-N,O)(1,10-phenanthroline-N,N')­copper(II) trihydrate complex was synthesized through the slow evaporation method. The crystal's structural, thermal, magnetic, and vibrational properties were obtained by X-ray powder diffraction (XRPD), thermal analyses, magnetization, Raman, and Fourier-transform infrared (FT-IR) spectroscopy. XRPD results showed that the crystalline complex belongs to a monoclinic system (P21/n). Thermal analyses revealed that around 333 K, the material undergoes a thermodynamically irreversible process. Magnetic data showed a paramagnetic behavior with weak ferromagnetic interactions. Moreover, all the Raman- and infrared-active bands were assigned from computational calculations based on the density functional theory (DFT) to analyze intra-molecular vibrational modes. In addition, the cytotoxic assay on colorectal cancer cells was performed to evaluate the antitumor activity of this ternary compound. Therefore, the antineoplastic activity of [Cu(1,10-phenanthroline)(glycine)Cl]•3H2O complex in HCT-116 cells was confirmed, showing a potent cytotoxic effect.

Bacillus thuringiensis: From biopesticides to anticancer agents.

Bacillus thuringiensis (Bt) is a ubiquitous bacterium that produces several proteins that are toxic to different invertebrates such as insects, nematodes, mites, and also some protozoans. Among these, Cry and Cyt proteins are most explored as biopesticides for their action against agricultural pests and vectors of human diseases. In 2000, a group of researchers from Japan isolated parasporal inclusion proteins from B. thuringiensis, and reported their cytotoxic action against human leukemia. Later, other proteins with similar antitumor properties were also isolated from this bacterium and these cytotoxic proteins with specific activity against human cancer cells were named parasporins. At present, nineteen different parasporins are registered and classified in six families. These parasporins have been described to have specific in vitro antitumor activity against several cancer cell lines. The antitumor activity makes parasporins possible candidates as anticancer agents. Various research groups around the world are involved in isolating and characterizing in vitro antitumor activity of these proteins and many articles reporting such activities in detail have been published. However, there are virtually no data regarding the antitumor activity of parasporins in vivo. This review summarizes the properties of these potentially useful antitumor agents of natural origin, focusing on their in vivo activity thus also highlighting the importance of testing these proteins in animal models for a possible application in clinical oncology.

Spectral characterization and biological evaluation of biomolecules from the peels of three orange fruits: a comparative study / Caracterização espectral e avaliação biológica de biomoléculas das cascas de três frutos de laranja: um estudo comparativo

The present work was designed to investigate the presence of bioactive chemicals in the reaction mixtures (RMs) of peels of Valencia, Mandarin, and African navel oranges, through GC-MS and FT-IR studies. Limonene, a unique compound, is present in the RMs of the three orange peels. Moreover, hexadecanoic acid 2-hydroxy-1-(hydroxymethyl) ethyl ester was identified in the RMs of all the three-orange peels. The RM of Mandarin orange exhibited potent cytotoxic effect against MCF-7 ATCC human breast cancer cells (HBC). All the three RMs exhibited moderate antibacterial activity against the human pathogenic bacteria Staphylococcus aureus (ATCC 25923), Staphylococcus epidermidis (ATCC 12228), Enterococcus faecalis (ATCC 29212), Escherichia coli (ATCC 25922), Klebsiella pneumoniae (ATCC 700603), Salmonella choleraesis (ATCC 10708), Pseudomonas aeruginosa (ATCC 27853), and Proteus mirabilis (ATCC 299).

O presente trabalho almejou investigar a presença de produtos químicos bioativos nas misturas de reação (MRs) de cascas de Valência, Tangerina e laranja umbigo africana, por meio de estudos de GC-MS e FT-IR. Assim, constatou-se que limoneno, um composto único, está presente nos RMs das três cascas de laranja. Além disso, o éster 2-hidroxi1-(hidroximetil) etílico do ácido hexadecanóico foi identificado nos RMs de todas as cascas de três laranjas. A RM da tangerina exibiu potente efeito citotóxico contra células de câncer de mama humano (HBC) MCF-7 ATCC. Todos os três RMs exibiram atividade antibacteriana moderada contra as bactérias patogênicas humanas dos seguintes tipos: Staphylococcus aureus (ATCC 25923), Staphylococcus epidermidis (ATCC 12228), Enterococcus faecalis (ATCC 29212), Escherichia coli (ATCC 25922), Klebsiella pneumoniae (ATCC 700603), Salmonella choleraesis (ATCC 10708), Pseudomonas aeruginosa (ATCC 27853) e Proteus mirabilis (ATCC 299).

In vitro cytotoxicity assay of Fucoidan extracted from Turbinaria conoides against cancer cell lines MCF7, A549, and normal cell line L929

Abstract The main aim of the study is to quantify the cytotoxic property of the Fucoidan extracted from the Turbinaria conoides using the MTT assay with the standard fucose. Fucoidan was extracted using the soaked water method and it was determined using the HPLC procedure the obtained Test sample Fucoidan extracted from the Turbinaria conoides and standard fucose was subjected to the cytotoxicity assay against the MCF7 Human breast cancer cell line, A549 lung cancer cell line, and L929 normal mouse fibroblast cell line. From the results it was found that the Test sample showed good IC50 value for MCF7 cell line then A549 with an increasing concentration 24 hours incubation at 37°C The IC50 for MCF7 was 115.21 µg/ml and A549 396.46µg/ml and the Fucoidan extract was checked for its cytotoxicity against the normal mouse fibroblast cell line L929, Fucoidan was found non-lethal to the L929 mouse fibroblast normal cell line. Standard fucose also gave a significant result towards MCF7 and against the L929. This indicates that the Fucoidan extracted from Tubinaria conoides shows better anticancer potential in it. Hence its application can be further extended in the pharmacological fields.

Fish Cytolysins in All Their Complexity.

The majority of the effects observed upon envenomation by scorpaenoid fish species can be reproduced by the cytolysins present in their venoms. Fish cytolysins are multifunctional proteins that elicit lethal, cytolytic, cardiovascular, inflammatory, nociceptive, and neuromuscular activities, representing a novel class of protein toxins. These large proteins (MW 150-320 kDa) are composed by two different subunits, termed α and ß, with about 700 amino acid residues each, being usually active in oligomeric form. There is a high degree of similarity between the primary sequences of cytolysins from different fish species. This suggests these molecules share similar mechanisms of action, which, at least regarding the cytolytic activity, has been proved to involve pore formation. Although the remaining components of fish venoms have interesting biological activities, fish cytolysins stand out because of their multifunctional nature and their ability to reproduce the main events of envenomation on their own. Considerable knowledge about fish cytolysins has been accumulated over the years, although there remains much to be unveiled. In this review, we compiled and compared the current information on the biochemical aspects and pharmacological activities of fish cytolysins, going over their structures, activities, mechanisms of action, and perspectives for the future.

Lignin from Morinda citrifolia leaves: Physical and chemical characterization, in vitro evaluation of antioxidant, cytotoxic, antiparasitic and ultrastructural activities.

In this work, we investigated in vitro the antioxidant, cytotoxic and anti-leishmanial activities of a lignin extracted from the leaves of Morinda citrifolia. Initially, an analysis of the composition of the sheets was performed, then the lignin was obtained by alkaline delignification and characterized by different techniques: elemental analysis, FT-R, UV-vis, HSQC-NMR, thermal analysis, Py-GC/MS and by GPC. The results showed that the leaves had in their composition cellulose (31.29%), hemicellulose (25.01%), lignin (18.34%), extractives (14.39%) and ash (10.03%). The lignin extraction yield was 89.8%. The lignin obtained is of the GSH type with the following contents 79.39%, 13.58% and 7.03% respectively. Furthermore, it is low molecular weight and thermally stable. It had a phenolic content of 93.3 mg GAE/g and low antioxidant activity. In macrophage cytotoxicity assays, it presented a CC50 of 31.0 µg/mL, showing less toxicity than amphotericin B. In assays against the promastigote forms of Leishmania amazonensis, lignin presented an IC50 of 29.56 µg/mL, a less effective concentration than amphotericin B (IC50 = 0.14 µg/mL). However, it was able to promote inhibition of the parasites, a fact confirmed by structural changes. These findings reinforce that M. citrifolia lignin is a promising macromolecule for use as an antiparasitic and antioxidant agent.

Synthetic enamine naphthoquinone derived from lawsone as cytotoxic agents assessed by in vitro and in silico evaluations.

We synthesized ten enamine naphthoquinones with yields ranging from 43 to 76%. These compounds were screened for their in vitro antiproliferative activities by MTT assay against four types of human cancer cell lines: HCT116, PC3, HL60 and SNB19. The naphthoquinones bearing the picolylamine (7) and quinoline (12) moieties were the most actives (IC50 < 24 µM for all the cell lines), which were comparable or better to the values obtained for the control drugs. In silico evaluations allowed us to develop a qualitative Structure-Activity Relationship which suggest that electrostatic features, particularly the C2-C3 internuclear repulsion and the molecular dipole moment, relate to the biological response. Furthermore, Molecular Docking simulations indicate that the synthetic compounds have the potential to act as anticancer molecules by inhibiting topoisomerase-II and thymidylate synthase.