Improvement of in vivo anticancer and antiangiogenic potential of thalidomide derivatives

AbstractThe strategy of antiangiogenic drugs is based on inhibiting formation of new blood vessels as alternative to limit cancer progression. In this work, we investigated the antitumor and antiangiogenic potential of eight thalidomide derivatives. Most of the molecules was not cytotoxic but 2a, 2d and 3d revealed weak antiproliferative activity on HL-60, Sarcoma 180 (S180) and normal peripheral blood mononuclear cells. Thalidomide, 2a and 2b were able to inhibit tumor growth (53.5%, 67.9% and 67.4%, respectively) in S180-bearing mice and presented moderate and reversible toxicity on liver, kidneys and spleens. Both analogs (2a and 2b) inhibited cell migration of endothelial (HUVEC) and melanoma cells (MDA/MB-435) at 50μg/mL. Immunohistochemistry labeling assays with CD-31 (PECAM-1) antibody showed microvascular density (MVD) was significantly reduced in thalidomide, 2a and 2b groups (30±4.9, 64.6±1.8 and 46.5±19.5%, respectively) (p<0.05). Neovascularization evaluated by Chorioallantoic Membrane Assay (CAM) with compounds 2a and 2b showed reduction of vessels’ number (12. 9±2.3 and 14.8±3.3%), neovascularization area (13.1±1.7 and 14.3±1.7%) and total length of vessels (9.2±1.5 and 9.9±1.9%). On the other hand, thalidomide did not alter vascularization parameters. Consequently, addition of thiosemicarbazone pharmacophore group into the phthalimidic ring improved the in vivo antitumor and antiangiogenic potential of the analogs 2a and 2b

Involvement of intrinsic mitochondrial pathway in neosergeolide-induced apoptosis of human HL-60 leukemia cells: The role of mitochondrial permeability transition pore and DNA damage

Context: Quassinoids are biologically active secondary metabolites found exclusively in the Simaroubaceae family of plants. These compounds generally present important biological properties, including cytotoxic and antitumor properties. Objective: In the present study, the cytotoxic effects of neosergeolide, a quassinoid isolated from Picrolemma sprucei Hook. f., were evaluated in human promyelocytic leukemia cells (HL-60). Materials and methods: Cytotoxicity and antiproliferative effects were evaluated by the MTT assay, May-Grünwald-Giemsa's staining, BrdU incorporation test, and flow cytometry procedures. The comet assay and micronuclei analysis were applied to determine the genotoxic and mutagenic potential of neosergeolide. Results: After 24h exposure, neosergeolide strongly inhibited cancer cell proliferation (IC 50 0.1 μM), and its activity seemed to be selective to tumor cells because it had no antiproliferative effect on human peripheral blood mononuclear cells (PBMC) at tested concentrations. Apoptosis was induced at submicromolar concentrations (0.05, 0.1, and 0.2 μM) as evidenced by morphological changes, mitochondrial depolarization, phosphatidylserine externalization, caspases activation, and internucleosomal DNA fragmentation. Additionally, neosergeolide effects were prevented by cyclosporine A (CsA), an inhibitor of the mitochondrial permeability transition (MPT) pore, which reinforced the participation of intrinsic pathways in the apoptotic process induced by this natural quassinoid. Direct DNA damage was further confirmed by comet assay and cytokinesis-block micronucleus test. Discussion and conclusion: The present study provided experimental evidence to support the underlying mechanism of action involved in the neosergeolide-mediated apoptosis. In addition, no antiproliferative effect or DNA damage effect of neosergeolide was evident in PBMC, highlighting its therapeutic potential. © 2012 Informa Healthcare USA, Inc

In vivo antitumoural activity and composition of an oil extract of Brazilian propolis

AbstractThe present study aimed to evaluate in vivo and in vitro the antitumoural activity of a propolis extract obtained with edible vegetable oil and its fractions and also to investigate its chemical composition by LC–MS and LC–MS/MS. To evaluate the toxicological aspects related to the propolis extract treatment, hematological, biochemical, histopathological and morphological analyses of treated animals were performed. All propolis extracts showed an in vivo antitumour activity in the experimental model with a moderate toxicity effect at experimental exposure levels. The oil extract was as effective as the ethanolic extract at inhibiting tumour growth. In vitro assays showed that the whole oil extract produced better inhibition of tumour cells than its fractions. LC–MS and LC–MS/MS identified four phenolic acids and three flavonoids. The anticancer potential of the oil extract of propolis has been demonstrated and the edible vegetable oil was shown as an attractive alternative solvent to extract bioactive natural propolis components

Perfil de flavonoides e avaliação do potencial antioxidante e citotóxico de Bauhinia purpurea (Fabaceae) da região amazônica

Bauhinia purpurea (Fabaceae). Plants of the Bauhinia species (Fabaceae) are used in the treatment of several infections and diseases, especially diabetes. In this paper, with an aim to contribute to the knowledge of the chemistry and therapeutic potential of the Amazonian species of the genus Bauhinia, flavonoid profiles in the leaves and branches of Bauhinia purpurea collected in Manaus and São Gabriel da Cachoeira/AM were analyzed by HPLC-DAD and ESIMS. Differences in the flavonoid profiles were detected along with the presence of rutin and isoquercitrin in the leaves collected in Manaus. All samples showed antioxidant activity, however, no cytotoxic activity against cell lines MDA-MB435 (breast), HCT-8 (colon), and SF-295 (glioblastoma) could be detected

Replacement of soybean meal with babassu meal in rations for broilers from 22 to 42 days old

O objetivo deste trabalho foi avaliar a viabilidade técnica e econômica da substituição parcial do farelo de soja pela torta de babaçu em rações para frangos de corte dos 22 aos 42 dias de idade. Foram utilizados 80 frangos Cobb 500®, distribuídos em delineamento inteiramente casualizado, com quatro tratamentos (0, 10, 20 e 30% de substituição do farelo de soja pela torta de babaçu) e cinco repetições de quatro aves. Foram avaliados o desempenho (ganho de peso, consumo de ração e conversão alimentar), rendimentos de carcaça e cortes, biometria dos órgãos, custo com alimentação por kg de frango produzido e margem bruta. Para verificar as relações de custo da substituição do farelo de soja pela torta de babaçu, foram estabelecidas inequações. Os níveis de substituição do farelo de soja pela torta de babaçu não influenciaram (P>0,05) nenhuma das características de desempenho, o que evidenciou a viabilidade técnica da substituição de até 30% do alimento. Da mesma forma, não houve efeito sobre os rendimentos de carcaça, cortes e biometria dos órgãos. O menor custo com alimentação por kg de frango produzido e a maior margem bruta foram obtidos com a utilização da ração contendo 0% de torta de babaçu. O aumento do nível de substituição do farelo de soja pela torta de babaçu, nas rações para frangos de corte dos 22 aos 42 dias de idade mostrou-se economicamente inviável, porém, as inequações elaboradas podem ser de grande utilidade em situações práticas.The objective this work was to evaluate the technical and economic viability of the substitution level of soybean meal by babassu meal in rations to broiler from 22 to 42 days old. It was used 80 male broiler chicks at one day of age, distributed into complete random designs with four treatments (0, 10, 20 e 30% substituition of soybean meal by babassu meal) and five repetitions of four broilers each. Were evaluated the performance (weight dain, feed intake and feed conversion), carcass and cuts, organ biometry, feed cost per kilogram body weight and gross margin. To verify the relationship of cost of replacing soybean meal with pie babassu, inequalities were established. The substitution level of soybean meal by babassu meal had no influence (P>0,05) any of the performance characteristics, wich showed the technical viability of substituting up to 30%. Similarly, there was no affect on carcass yield, cuts weight and organ biometry. The cust less with feed per kg for chicken produced and the higher gross margin were obtained from chickens fed diets with 0% babassu meal. The increased of substitution level soybean meal by babassu meal in ration for broilers from 22 to 42 days old proved unviable economically, however, the inequalities produced can be useful in practical situations

Replacement of corn with babassu mesocarp flour in balanced rations for broilers in the period from 1 to 21 days

The objective of this study was to evaluate the technical and economic feasibility of partial replacement of corn with babassu mesocarp flour in diets for broilers from one to 21 days of age. Two hundred male day-old chicks, from the Cobb 500® line, were distributed in a completely randomized design with four treatments (0%, 10%, 20% and 30% replacement of maize flour with the babassu mesocarp) and five replicates were used comprising ten birds. Were evaluated performance (weight gain, feed intake, feed conversion and water intake), organ biometrics, metabolizability coefficients of dry matter (MCDM), crude protein (MCCP) and gross energy (MCGE) and cost of feeding diets containing babassu mesocarp flour (BMF). It was observed that the substitution of corn with BMF negatively influenced (P 0.05) the relative weights of the carcass, bursa, spleen, heart, gizzard or liver, nor the relative weight or length of the small intestine. The lower cost of feed per kg of weight gain was obtained with the diet containing 10% corn replacement with BMF, which resulted in a higher gross margin in relation to food. The replacement of corn with BMF in diets for broilers from one to 21 days of age proved to be technically feasible in 10%