Analysis of metabolic compounds and antitumorigenic effects of Albizia niopoides and Senegalia polyphylla leaves.

The objective of this study was to quantify metabolic compounds in leaves of A. niopoides and S. polyphylla and to evaluate the antitumor potential of extracts from both species in cervical tumour cells. The physiological analyses performed were quantification of starch, sucrose, phenolic compounds and proteins. An aqueous extract was prepared and added to the SiHa cell line at concentrations of 10, 100 and 1000 µg/mL at 4h, 24h, 48h and 72h. Cell morphology, proliferation and viability were analysed. The species showed a large amount of starch and phenolic compounds. Treatment with the extract of both species caused morphological changes in SiHa cells and exhibited antiproliferative effects at a concentration of 1000 µg/ml. In cell viability test, only A. niopoides showed a significant reduction. The study presented the effects of the species against a cervical cancer cell line, where A. niopoides has already shown to be a promising plant drug.

Chemical Composition, In Vitro Antitumor Effect, and Toxicity in Zebrafish of the Essential Oil from Conyza bonariensis (L.) Cronquist (Asteraceae).

The essential oil from Conyza bonariensis (Asteraceae) aerial parts (CBEO) was extracted by hydrodistillation in a Clevenger-type apparatus and was characterized by gas chromatography-mass spectrometry. The antitumor potential was evaluated against human tumor cell lines (melanoma, cervical, colorectal, and leukemias), as well as non-tumor keratinocyte lines using the MTT assay. The effect of CBEO on the production of Reactive Oxygen Species (ROS) was evaluated by DCFH-DA assay, and a protection assay using the antioxidant N-acetyl-L-cysteine (NAC) was also performed. Moreover, the CBEO toxicity in the zebrafish model was assessed. The majority of the CBEO compound was (Z)-2-lachnophyllum ester (57.24%). The CBEO exhibited selectivity towards SK-MEL-28 melanoma cells (half maximal inhibitory concentration, IC50 = 18.65 ± 1.16 µg/mL), and induced a significant increase in ROS production. In addition, the CBEO's cytotoxicity against SK-MEL-28 cells was reduced after pretreatment with NAC. Furthermore, after 96 h of exposure, 1.5 µg/mL CBEO induced death of all zebrafish embryos. Non-lethal effects were observed after exposure to 0.50-1.25 µg/mL CBEO. Additionally, significant alterations in the activity of enzymes associated with oxidative stress in zebrafish larvae were observed. These results provide evidence that CBEO has a significant in vitro antimelanoma effect by increasing ROS production and moderate embryotoxicity in zebrafish.

Comparison of Phytochemical Composition and Untargeted Metabolomic Analysis of an Extract from Cnidoscolus aconitifolius (Mill.) I. I. Johnst and Porophyllum ruderale (Jacq.) Cass. and Biological Cytotoxic and Antiproliferative Activity In Vitro.

Cnidoscolus aconitifolius (CA) and Porophyllum ruderale (PR) are representative edible plants that are a traditional food source in Mexico. This research aimed to analyze the phytochemical composition and untargeted metabolomics analysis of CA and PR and evaluate their antiproliferative effect in vitro. The phytochemical composition (UPLC-DAD-QToF/MS-ESI) identified up to 38 polyphenols and selected organic acids that were clustered by the untargeted metabolomics in functional activities linked to indolizidines, pyridines, and organic acids. Compared with PR, CA displayed a higher reduction in the metabolic activity of human SW480 colon adenocarcinoma cells (LC50: 10.65 mg/mL), and both extracts increased the total apoptotic cells and arrested cell cycle at G0/G1 phase. PR increased mRNA Apc gene expression, whereas both extracts reduced mRNA Kras expression. Rutin/epigallocatechin gallate displayed the highest affinity to APC and K-RAS proteins in silico. Further research is needed to experiment on other cell lines. Results suggested that CA and PR are polyphenol-rich plant sources exhibiting antiproliferative effects in vitro.

Gold Nanoparticles Synthesized with Common Mullein (Verbascum thapsus) and Castor Bean (Ricinus communis) Ethanolic Extracts Displayed Antiproliferative Effects and Induced Caspase 3 Activity in Human HT29 and SW480 Cancer Cells.

Gold nanoparticles (AuNPs) are promising nanomaterials exhibiting anti-cancer effects. Green AuNPs synthesis using plant extracts can be used to achieve stable and beneficial nanoparticles due to their content of bioactive compounds. This research aimed to synthesize and evaluate the antiproliferative and caspase-3 activity induction of green AuNPs synthesized with common mullein (V. thapsus) flowers (AuNPsME) and castor bean (R. communis) leaves (AuNPsCE) ethanolic extracts in human HT29 and SW480 colorectal cancer cells. Their effect was compared with chemically synthesized AuNPs (AuNPsCS). The extracts mainly contained p-coumaric acid (71.88-79.93 µg/g), ferulic acid (19.07-310.71 µg/g), and rutin (8.14-13.31 µg/g). The obtained nanoparticles presented typical FT-IR bands confirming the inclusion of polyphenols from V. thapsus and R. communis and spherical/quasi-spherical morphologies with diameters in the 20.06-37.14 nm range. The nanoparticles (20-200 µg/mL) showed antiproliferative effects in both cell lines, with AuNPsCE being the most potent (IC50 HT29: 110.10 and IC50SW480: 64.57 µg/mL). The AuNPsCS showed the lowest intracellular reactive oxygen species (ROS) generation in SW480 cells. All treatments induced caspase 3/7 activity to a similar or greater extent than 30 mM H2O2-treated cells. Results indicated the suitability of V. thapsus and R. communis extracts to synthesize AuNPs, displaying a stronger antiproliferative effect than AuNPsCS.

Review of Therapies using TiO2 Nanomaterials for Increased Anticancer Capability.

Recently, Titanium dioxide (TiO2) has been studied as an alternative to treat cancer diseases under different activation therapies. The aim of this review was to describe the effect of TiO2 nanoparticles (NPs) on some cancer cell lines and their interaction with phototherapies such as photodynamic therapy (PDT), photothermal therapy (PTT), sonodynamic therapy (SDT), and ultraviolet therapy (UV) for anticancer treatment. The use of TiO2 combined with PDT, PTT, SDT, or UV has shown a remarkable capacity to enhance the killing of cancer cells through reactive oxygen species formation. Thus, the combination of TiO2 and activation therapies exhibited great potential and could be a viable anticancer treatment strategy. However, more studies on phototherapies in combination with TiO2 and their effects under different experimental conditions (TiO2 concentration, type of cancer cells, and intensity and frequency of therapies) are necessary to guarantee the safe use of this kind of therapy.

The toxicity of Aspidosperma subincanum to MCF7 cells is related to modulation of oxidative status and proinflammatory pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Cancer is an inflammatory disease because carcinogenesis and tumor progression depend on intrinsic and extrinsic inflammatory pathways. Although species of the genus Aspidosperma are widely used to treat tumors, and there is ethnopharmacological evidence for traditional use of the species A. subincanum as an anti-inflammatory agent, its antineoplastic potential is unknown. AIM OF THE STUDY: To evaluate toxic effects of the indole alkaloid-rich fraction (IAF) of A. subincanum on the MCF7 cell line and identify some of the anti-inflammatory mechanisms involved. MATERIALS AND METHODS: Chromatographic analyses were performed by ultra-high-performance liquid chromatography with electrospray ionization mass spectrometry, and cytotoxic and antiproliferative effects of IAF were verified by MTT and clonogenic assays. Cell cycle alterations were analyzed by measuring DNA content, while propidium iodide and acridine orange staining was performed to determine the type of induced cell death. The expression of apoptosis markers and proteins involved in cell proliferation and survival pathways was analyzed by immunoblotting, RT-qPCR, and ELISAs. Interference with redox status was investigated using a DCFH-DA probe and by measuring catalase activity. RESULTS: Chromatographic analyses showed that IAF is a complex mixture containing indole alkaloids. IAF selectively exerted toxic and antiproliferative effects, elevating the Bax/Bcl-xL ratio and inducing apoptosis in MCF7 cells. IAF decreased intracellular reactive oxygen species levels and increased catalase activity, while reducing the IL-8 level and suppressing COX-2 expression. CONCLUSIONS: IAF induces apoptosis in MCF7 cells by suppressing COX-2 expression while reducing IL-8 levels and intracellular content of reactive oxygen species.

Phenolic compounds of blueberries (Vaccinium spp) as a protective strategy against skin cell damage induced by ROS: A review of antioxidant potential and antiproliferative capacity.

The skin is a tissue with a high metabolic activity that acts as a protective layer for the internal organs of the body. This tissue is exposed to a variety of damaging agents, including reactive oxygen species (ROS), which can lead to oxidative damage to various macromolecules, disrupting vital cellular processes and increasing mutations. A situation referred to as oxidative stress occurs when a large amount of oxidants exceeds the capacity of the antioxidant defense system. Oxidative stress is considered a contributory factor to the aging process and the pathogenesis of various skin diseases, including cancer. Several current studies seek to identify new natural compounds with properties that mitigate the harmful effects of ROS, thereby acting as blockers or suppressors of the carcinogenesis process. This review briefly presents the relationship between ultraviolet radiation, ROS, and skin damage; and summarizes the in vitro and in vivo experimental evidence of the chemopreventive effect on skin cancer of phenolic compounds from blueberries (Vaccinium spp). Although several studies addressed the topic of bioactive compounds and their activities as possible anticancer agents, none have focused on the antioxidative action and antiproliferative effects on skin cancer of phenolic compounds derived from blueberries.

Chemical composition, antiproliferative and antioxidant attributes of ethanolic extract of resinous sediment from Etlingera elatior (Jack. ) inflorescence

The ethanolic extract of resinous sediment (EERS) of Etlingera elatior young inflorescence was examined for its anticancer effect and potential antioxidant activity. The anticancer effect of the EERS was evaluated on four human cancer cell lines, HCT 116, HT-29, Hela, and MCF-7, using the MTT assay. GC-MS analysis showed that the main components found in the EERS were nonyl cyclopropane (4.44%), 1-tetradecane (3.66%), cyclotetradecane (2.41%), cyclododecane (1.92%), and 1-decene (1.72%). The antioxidant activity was determined through different methods. High amounts of TPC and TFC in the EERS were found. Moderate antioxidant capacity of the EERS was detected by DPPH and ABTS assays, with EC50 values of 44.19 and 56.61 µg/mL and a high FRAP value of 281.79 nmol Fe+2 equivalent/mg extract. In the MTT assay, the EERS showed potent anticancer activity, with IC50 values of 19.82, 37.001, 50.49, and 53.29 µg/mL against HT-29, HCT 116, Hela, and MCF-7 tumour cell lines, respectively. Moreover, the results were comparable to or less potent than the standard reference drug, 5-fluorouracil. The results showed that the EERS of Etlingera elatior inflorescence contained a high amount of polyphenols and flavonoids, which may to the selective antiproliferative effects towards colon cancer in vitro

Seasonality Modulates the Cellular Antioxidant Activity and Antiproliferative Effect of Sonoran Desert Propolis.

The main chemical composition and pharmacological potential of propolis from arid and semi-arid regions of the Sonoran Desert have been previously reported. Caborca propolis (CP), from an arid zone of the Sonoran Desert, has shown a polyphenolic profile that suggests a mixed plant origin, presenting poplar-type markers, as well as a 6-methoxylated flavonoid, xanthomicrol, characteristic of Asteraceae plants. In addition, CP has shown significant antioxidant properties and antiproliferative activity on cancer cells. In this study, we analyzed the influence of collection time on the chemical constitution, antiproliferative activity and protective capacity of CP against reactive oxygen species (ROS), by using HPLC-UV-diode array detection (DAD) analysis, 3-(4,5-dimethylthiazol-2-yl)-2,5-Dimethyltetrazoliumbromide (MTT) and 2,2-diphenyl-1-picryl-hydrazyl (DPPH) assays, as well as cellular antioxidant activity (CAA) assay on murine B-cell lymphoma M12.C3.F6 cells. HPLC-UV-DAD analyses of seasonally collected CP (one-year period) revealed quantitative differences among the most abundant CP constituents: pinocembrin, galangin, chrysin and pinobanksin-3-O-acetate. Though all seasonal samples of CP induced an antiproliferative effect in M12.C3.F6 cells, CP from autumn showed the highest inhibitory activity (IC50: 5.9 ± 0.6 µg/mL). The DPPH assay pointed out that CP collected in autumn presented the highest antioxidant potential (IC50: 58.8 ± 6.7 µg/mL), followed by winter (65.7 ± 12.2 µg/mL) and spring (67.0 ± 7.5 µg/mL); meanwhile, the summer sample showed a lesser antioxidant capacity (IC50: 98.7 ± 2.5 µg/mL). The CAA assay demonstrated that CP induced a significant protective effect against ROS production elicited by H2O2 in M12.C3.F6 cells. Pretreatment of M12.C3.F6 cells with CP from spring and autumn (25 and 50 µg/mL for 1 h) showed the highest reduction in intracellular ROS induced by H2O2 (1 and 5 mM). These results indicate that the antiproliferative effect and cellular antioxidant activity of CP are modulated by quantitative fluctuations in its polyphenolic profile due to its collection time.

Antiproliferative Effect of Amaranth Proteins and Peptides on HT-29 Human Colon Tumor Cell Line.

Antiproliferative effect of Amaranthus mantegazzianus proteins and peptides released after simulated gastrointestinal digestion (DH% 37.8 ± 3.8) was investigated on human colon cancer cell line HT-29. Inhibition of proliferation of HT-29 cells was exhibited after a 24 h treatment with different concentrations of amaranth protein isolate (API) and the peptides released after digestion (DGS), presenting IC50 values of 1.35 ± 0.12 and 0.30 ± 0.07 mg soluble protein/mL, respectively. Lactate dehydrogenase assay indicated that both samples caused the loss of membrane integrity and cell lysis over HT-29 cells, and DAPI fluorescence microscopies evidenced typical apoptotic features. Moreover, Annexin V-FITC flow cytometry showed a significant increase of early apoptotic and late apoptotic/necrotic HT-29 cells compared to untreated ones, and caspase-3 assay confirmed the apoptosis induction with a 43.0 ± 10.3 and 65.8 ± 12.7% increase of caspase-3 activity produced by a 2 mg/mL treatment of API and DGS, respectively. In conclusion, amaranth peptides successfully released after simulated gastrointestinal digestion would exert a potential antiproliferative activity over HT-29 tumor cells. This effect was linked to the induction of cell necrosis and apoptosis, supporting the idea of using amaranth proteins as a potential food alternative ingredient for functional foods.

Silver/silver chloride nanoparticles inhibit the proliferation of human glioblastoma cells.

Glioblastomas (GBM) are aggressive brain tumors with very poor prognosis. While silver nanoparticles represent a potential new strategy for anticancer therapy, the silver/silver chloride nanoparticles (Ag/AgCl-NPs) have microbicidal activity, but had not been tested against tumor cells. Here, we analyzed the effect of biogenically produced Ag/AgCl-NPs (from yeast cultures) on the proliferation of GBM02 glioblastoma cells (and of human astrocytes) by automated, image-based high-content analysis (HCA). We compared the effect of 0.1-5.0 µg mL-1 Ag/AgCl-NPs with that of 9.7-48.5 µg mL-1 temozolomide (TMZ, chemotherapy drug currently used to treat glioblastomas), alone or in combination. At higher concentrations, Ag/AgCl-NPs inhibited GBM02 proliferation more effectively than TMZ (up to 82 and 62% inhibition, respectively), while the opposite occurred at lower concentrations (up to 23 and 53% inhibition, for Ag/AgCl-NPs and TMZ, respectively). The combined treatment (Ag/AgCl-NPs + TMZ) inhibited GBM02 proliferation by 54-83%. Ag/AgCl-NPs had a reduced effect on astrocyte proliferation compared with TMZ, and Ag/AgCl-NPs + TMZ inhibited astrocyte proliferation by 5-42%. The growth rate and population doubling time analyses confirmed that treatment with Ag/AgCl-NPs was more effective against GBM02 cells than TMZ (~ 67-fold), and less aggressive to astrocytes, while Ag/AgCl-NP + TMZ treatment was no more effective against GBM02 cells than Ag/AgCl-NPs monotherapy. Taken together, our data indicate that 2.5 µg mL-1 Ag/AgCl-NPs represents the safest dose tested here, which affects GBM02 proliferation, with limited effect on astrocytes. Our findings show that HCA is a useful approach to evaluate the antiproliferative effect of nanoparticles against tumor cells.

Novel selenylated imidazo[1,2-a]pyridines for breast cancer chemotherapy: Inhibition of cell proliferation by Akt-mediated regulation, DNA cleavage and apoptosis.

A novel series of selenylated imidazo[1,2-a]pyridines were designed and synthesized with a view to a promising activity against breast cancer cell. The compounds, 7-methyl-3-(naphthalene-1-ylselanyl)-2-phenylimidazo[1,2-a]pyridine, named IP-Se-05, and 3-((2-methoxyphenyl)selanyl)-7-methyl-2-phenylimidazo[1,2-a]pyridine, named IP-Se-06, showed high cytotoxicity for MCF-7 cells (IC50 = 26.0 µM and 12.5 µM, respectively). Both the compounds inhibited the cell proliferation and caused decrease in the number of cells in the G2/M phase of cell cycle. IP-Se-05 and IP-Se-06 were also evaluated for effects on CT-DNA and DNA of MCF-7 cells. The compounds intercalated into CT-DNA and both treatments caused cleavage of DNA in cells. In addition, the compounds induced cell death by apoptosis. However, the presence of (2-methoxyphenyl) selenyl moiety at the imidazo[1,2-a]pyridine (IP-Se-06) appears to have a better antitumor effect with higher cytotoxicity at a lower concentration and caused less necrosis. Overall, the current study established IP-Se-06 more than IP-Se-05 as a potential prototype compound to be employed as an antiproliferative agent for the treatment of breast cancer.

Oligostilbenoids in Vitis vinifera L. Pinot Noir grape cane extract: Isolation, characterization, in vitro antioxidant capacity and anti-proliferative effect on cancer cells.

The following oligostilbenoids were isolated from extracts of Vitis vinifera L. Pinot Noir grape canes produced at a pilot-plant scale: (E)-ε-viniferin, (E)-resveratrol, (E)-piceatannol, ampelopsin A, vitisin B, pallidol, (E)-δ-viniferin, (E)-ω-viniferin, (E)-trans-cis-miyabenol C, isorhapontigenin, scirpusin A, and a new isomer named isoscirpusin A. The antioxidant capacity of the isolated stilbenoids was studied by three different assays, and their 50% inhibition concentration (IC50) against cancer cells was determined by MTT reduction assay. Besides (E)-resveratrol, stilbenoids have outstanding antioxidant capacity in the ORAC-FL assay. The strongest antiproliferative effect was observed for (E)-piceatannol and ampelopsin A against the bladder cancer cell line J82. (E)-Piceatannol has inhibitory effect on human lung cancer SK-MES-1 cells. Moreover, the whole extract has antiproliferative effect on all tested cell lines. In conclusion, beside (E)-resveratrol, grape cane extract contains oligostilbenoids with potential health benefits. This underexploited viticultural residue has the potential to produce valuable phytochemicals or ingredients in functional foods.

Leaf anatomy of Protium ovatum and its antiproliferative potential in cervical cells

ABSTRACT The aim of this study was to analyze the morphology and anatomy of the leaves of Protium ovatum Engl., Burseraceae, and verify the antiproliferative activity in cervical cells. For anatomical analysis, the leaf samples were fixed in formol, acetic acid, alcohol 70, dehydrated, included in hydroxyethyl methacrylate and sectioned at a thickness of 5-10 µm in rotative microtome. The samples were stained with toluidine blue and blades mounted with synthetic resin "Entellan". Histochemical tests and scanning electron microscopy were also performed. To investigate the antiproliferative effect we used the cells strain of human cervix carcinoma and normal keratinocytes. The anatomical analysis demonstrated that the leaf is hypostomatic and the epidermal cells walls were slightly undulate on both faces. The palisade parenchyma occupies most part of leaf mesophyll. The spongy parenchyma is organized into 3-4 layers of cells. Vascular bundles of smaller diameter and secretory cavities are distributed along the leaf mesophyll. The midrib region was formed by a single vascular bundle with xylem in the center surrounded by phloem. Secretory cavities are distributed along the phloem. The histochemical tests revealed the presence of lipids in the secretory cavities and phenolic compounds in almost cell of mesophyll. Scanning electron microscopy analysis showed the smooth leaf cuticle ornamentation with some striated areas. It was observed antiproliferative effect on human cervix carcinoma cell comparing with normal cells.

Toxicity of Jatropha curcas L. latex in Allium cepa test / Toxicidade do látex de Jatropha curcas L. no modelo de Allium cepa

The latex obtained from Jatropha curcas (physic nut) is used in traditional medicine to treat a variety of disturbs, including burns, hemorrhoids, ringworm and ulcers. Phytochemical analyses have shown that J. curcas latex contains natural compounds with therapeutic potential. In this study, the toxicity, cytotoxicity and genotoxicity effects of J. curcas latex on the root cells of Allium cepa were examined. Onion seeds and bulbs were exposed to seven different concentrations of latex and then the roots were submitted to macro and microscopic analyses. Water and sodium azide were used as negative and positive controls, respectively. The analysis of root growth showed that J. curcas crude latex or 50% diluted is highly toxic. Cytogenetic results showed that the mitotic index of the onion roots submitted to latex treatment decreased significantly compared to the negative control, which suggests that the latex is cytotoxic. High incidence of chromosome aberrations in the cells treated with J. curcas latex was observed too, indicating that the latex also presents genotoxic effect. The analyses presented in this report suggest the toxic, cytotoxic and genotoxic effects of J. curcas latex. Then, the indiscriminate use of J. curcas latex in folk medicine could bring risk to human health.

O látex obtido de Jatropha curcas (pinhão manso) é usado na medicina tradicional para tratamento de diversos distúrbios, como queimaduras, hemorroida, micose e úlcera. Análises fitoquímicas apontaram que o látex de J. curcas contém compostos naturais com potencial terapêutico. Este estudo avaliou a toxicidade, citotoxicidade e genotoxicidade do látex de J. curcas em células da raiz de Allium cepa. Sementes e bulbos de cebola foram expostos á sete diferentes concentrações de látex e, então, as raízes foram submetidas a análises macro e microscópica. Água e azida sódica foram utilizadas como controle negativo e positivo, respectivamente. A análise do comprimento das raízes mostrou que o látex de J. curcas puro e diluído a 50% é altamente tóxico. O índice mitótico das raízes de cebola submetidas ao tratamento com o látex diminuiu significativamente comparado com o controle negativo, o que sugere que o látex é citotóxico. Uma alta incidência de aberrações cromossômicas em células tratadas com o látex de J. curcas também foi observada, indicando que o látex apresenta efeito genotóxico. Essa análise sugere que o látex de J. curcas possui efeitos tóxico, citotóxico e genotóxico, sendo que o uso indiscriminado do látex de J. curcas na medicina popular pode trazer risco à saúde humana.

Antimicrobial and Antiproliferative Activity of Bauhinia forficata Link and Cnidoscolus quercifolius Extracts commonly Used in Folk Medicine.

BACKGROUND: Bauhinia forficata and Cnidoscolus quercifolius plants are commonly used in folk medicine. However, few studies have investigated their therapeutic potential. AIM: Herein, we evaluated the antimicrobial activity of B. forficata and C. quercifolius extracts against microorganisms of clinical relevance and their antiproliferative potential against tumor cells. MATERIALS AND METHODS: The following tests were performed: Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC)/minimum fungicidal concentration (MFC), inhibition of biofilm adhesion, and effects on cell morphology. Antiproliferative tests were carried out with human keratinocytes and six tumor lines. RESULTS: Bauhinia forficata showed antimicrobial activity only against C. albicans with MIC of 15.62 ug/mL and MFC higher than 2000 ug/mL. It also inhibited biofilm adhesion and caused alterations in cell morphology. Cnidoscolus quercifolius showed no significant activity (MIC > 2.0 mg/mL) against the strains. Bauhinia forficata and C. quercifolius extracts showed cytostatic activity against the tumor cells. CONCLUSION: Bauhinia forficata has promising anti-Cand/da activity and should be further investigated for its therapeutic potential. CLINICAL SIGNIFICANCE: The use of medicinal plants in the treatment of infectious processes has an important function nowadays, due to the limitations of the use of synthetic antibiotics available, related specifically to the microbial resistance emergence.

The biochemical characterization, stabilization studies and the antiproliferative effect of bromelain against B16F10 murine melanoma cells.

The current study aims to extract bromelain from different parts (stem, crown, peels, pulp and leaves) of Ananas comosus var. comosus AGB 772; to determine of optimum pH and temperature; to test bromelain stability in disodium EDTA and sodium benzoate, and to investigate its pharmacological activity on B16F10 murine melanoma cells in vitro. The highest enzymatic activity was found in bromelain extracted from the pulp and peel. The optimum bromelain pH among all studied pineapple parts was 6.0. The optimum temperature was above 50 °C in all bromelain extracts. The fluorescence analysis confirmed the stability of bromelain in the presence of EDTA and sodium benzoate. Bromelain was pharmacologically active against B16F10 melanoma cells and it was possible verifying approximately 100% inhibition of tumor cell proliferation in vitro. Since bromelain activity was found in different parts of pineapple plants, pineapple residues from the food industry may be used for bromelain extraction.

Lupeol and its esters: NMR, powder XRD data and in vitro evaluation of cancer cell growth

ABSTRACT The triterpene lupeol (1) and some of its esters are secondary metabolites produced by species of Celastraceae family, which have being associated with cytotoxic activity. We report herein the isolation of 1, the semi-synthesis of eight lupeol esters and the evaluation of their in vitro activity against nine strains of cancer cells. The reaction of carboxylic acids with 1 and DIC/DMAP was used to obtain lupeol stearate (2), lupeol palmitate (3) lupeol miristate (4), and the new esters lupeol laurate (5), lupeol caprate (6), lupeol caprilate (7), lupeol caproate (8) and lupeol 3',4'-dimethoxybenzoate (9), with high yields. Compounds 1-9 were identified using FT-IR, 1H, 13C-NMR, CHN analysis and XRD data and were tested in vitro for proliferation of human cancer cell activity. In these assays, lupeol was inactive (GI50> 250µg/mL) while lupeol esters 2 -4 and 7 - 9 showed a cytostatic effect. The XRD method was a suitable tool to determine the structure of lupeol and its esters in solid state. Compound 3 showed a selective growth inhibition effect on erythromyeloblastoid leukemia (K-562) cells in a concentration-dependent way. Lupeol esters 4 and 9 showed a selective cytostatic effect with low GI50 values representing promising prototypes for the development of new anticancer drugs.

Metotrexato en condromatosis sinovial: una serendipia / Methotrexate in sinovial chondromatosis: a case of serendipity

La condromatosis sinovial es una metaplasia idiopática benigna de la membrana sinovial que afecta a 1/100.000 habitantes, en una relación hombre/mujer de 3 a 1 entre los 30 y 50 años. Predomina en grandes articulaciones como rodilla (70%), cadera (20%) y hombro (19%), y en menor proporción en codo y tobillo. Puede ser primaria o secundaria. La etiología es desconocida. La resolución es quirúrgica ya sea por artroscopia o por cirugía a cielo abierto, no existiendo otra alternativa terapéutica. Se presenta el caso clínico de un paciente con condromatosis sinovial en hombro derecho, que se comporta como una artropatía erosiva, indicándose metotrexato y resolviendo casi totalmente los nódulos condromatosos.

The synovial chondromatosis is a benign idiopathic metaplasia ofthe synovial membrane which affects one in 100,000 inhabitants. Itis 3 times more common in males, aged between 30 and 50 yearsold. It is commonly found in large joints such as knee (70%), hip(20%) and shoulder (19%) and less frequently in elbow and heel. Itcan be primary or secondary. The etiology is still unknown.The resolution is surgical by means of arthroscopy or open surgery,existing no other therapeutic alternatives.We present a male patient with primary synovial chondromatosis inthe right shoulder, leading to an erosive arthropathy. Treatment withmethotrexate resolved almost entirely the cartilaginous nodules.