Flow sorting and exome sequencing reveal the oncogenome of primary Hodgkin and Reed-Sternberg cells

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Inhibition of bladder cancer cell proliferation by allyl isothiocyanate (mustard essential oil)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Role of cyclooxygenase-2 in Trypanosoma cruzi survival in the early stages of parasite host-cell interaction

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Chemical composition and antiproliferative activity of Acalypha californica

Acalypha californica Benth., is a plant in the northwestern region from Mexico, commonly known as "cancer herb" and used in traditional medicine for treating cancer. In the present study we have investigated the antiproliferative activity of methanolic extract of A. californica and its fractions in cancer cell lines and phytochemical analysis and mechanism of apoptosis of the fractions with antiproliferative activity. The antiproliferative activity of methanol extract and its fractions of solvents were evaluated by MTT assay against the M12.A(k).C3.F6, RAW 264.7, HeLa and L929 cell lines. Active fractions were fractionated by molecular exclusion chromatography, HPLC and MPLC. The identification of compounds was performed by NMR and FIA-ESI-IT-MS/MS analysis. Apoptotic mechanism was analyzed by flow cytometry, determining the reduction in the mitochondrial membrane potential (JC-1) and the activity of caspases 3,8 and 9. Cell viability assays showed that the hexane fraction of the methanol extract of the plant has significant effects against cancer lines RAW 264.7 (IC50 = 52.08 +/- 1.06 mu g/mL) and HeLa (IC50 = 46.77 +/- 1.09 mu g/mL), the residual fraction showed a selective effect on cell lines M12.A(k).C3.F6 (IC50 = 59.90 +/- 1.05 mu g/mL), RAW 264.7 (IC50 = 58.93 +/- 1.26 mu g/mL) and HeLa (IC50 = 50.11 +/- 1.135 mu g/mL) compared to the control cell line L929 (IC50 = 100.00 +/- 1.09 mu g/mL). The chemical characterization of the active fractions allowed the identification of p-sitosterol and stigmasterol in hexane fraction and some phenolic acids, proanthocyanidins and flavonoids in the residual fraction. The methanol extract and hexane fraction reduces mitochondrial membrane potential significantly and activates caspases 3, 8 and 9. Because of the antiproliferative activity observed, our results provide a rational basis for the use of extracts of A. californica in treating various types of cancer in traditional medicine from Mexico. The extracts induce apoptosis via activation of caspases. (C) 2015 Elsevier B.V. All rights reserved.

In vitro effect of caffeic acid phenethyl ester on matrix metalloproteinases (MMP-1 and MMP-9) and their inhibitor (TIMP-1) in lipopolysaccharide-activated human monocytes

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Antiproliferative activity of cardenolide glycosides from Asclepias subulata

Asclepias subulata Decne. is a shrub occurring in Sonora-Arizona desert (Mexico-USA). The ethnic groups, Seris and Pimas, use this plant for the treatment of sore eyes, gastrointestinal disorders and cancer. To isolate the compounds responsible for antiproliferative activity of the methanol extract of A. subulata. A bioguided fractionation of methanol extract of A. subulata was performed using MTT assay to measure the antiproliferative activity of different compounds on three human cancer cell lines (A549, LS 180 and PC-3), one murine cancer cell line (RAW 264.7) and one human normal cell line (ARPE-19). The methanol extract was partitioned with hexane, ethyl acetate and ethanol. The active fractions, ethanol and residual, were fractioned by silica-column chromatography and active sub-fractions were separated using HPLC. The chemical structures of isolated compounds were elucidated with different chemical and spectroscopic methods. A new cardenolide glycoside, 12, 16-dihydroxycalotropin, and three known, calotropin, corotoxigenin 3-O-glucopyranoside and desglucouzarin, were isolated of active sub-fractions. All isolated compounds showed a strong antiproliferative activity in human cancer cells. Calotropin was the more active with IC50 values of 0.0013, 0.06 and 0.41 µM on A549, LS 180 and PC-3 cell lines, respectively; while 12, 16-dihydroxycalotropin reached values of 2.48, 5.62 and 11.70 µM, on the same cells; corotoxigenin 3-O-glucopyranoside had IC50 of 2.64, 3.15 and 6.62 µM and desglucouzarin showed values of 0.90, 6.57 and 6.62, µM. Doxorubicin, positive control, showed IC50 values of 1.78, 6.99 and 3.18 µM, respectively. The isolated compounds had a weak effect on murine cancer cells and human normal cells, exhibiting selectivity to human cancer cells. In this study, we found that 12, 16-dihydroxicalotropin, calotropin, corotoxigenin 3-O-glucopyranoside and desglucouzarin are responsible of antiproliferative properties of A. subulata, and that these compounds are highly selective to human cancer cells. Further studies are needed in order to establish the action mechanisms of the isolated compounds.

Tumour necrosis factor-alpha-induced protein 8 (TNFAIP8) expression associated with cell survival and death in cancer cell lines infected with canine distemper virus

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Potencial anti-inflamatório e antiproliferativo de compostos inibidores da enzima desoxi-hipusina sintase

Pós-graduação em Biotecnologia - IQ

Análise do efeito in vitro de acridonas na replicação do Vírus da Hepatite C

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Compostos de paládio(II) contendo ligantes N,S-quelantes: síntese, caracterização e investigação da atividade biológica

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Compostos de Pd(II) contendo ligantes N,S-doadores: síntese, caracterização e estudo da atividade citotóxica

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Modulação da atividade das interleucinas 17B e 25 associadas à melatonina como indutores de apoptose em cultivo celular de neoplasias mamárias

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Avaliação de atividades biológicas dos extratos de Rosmarinus officinalis L. (alecrim) e Thymus vulgaris L. (tomilho)

Pós-graduação em Biopatologia Bucal - ICT

Avaliação da ação da melatonina em células-tronco tumorais mamárias RE-positivas tratadas com disruptores estrogênicos: verificação da via do receptor de estrógeno mediada pelo gene OCT 4

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Leishmanicidal and cholinesterase inhibiting activities of phenolic compounds of Dimorphandra gardneriana and Platymiscium floribundum, native plants from Caatinga biome

Nos últimos anos, o Ministério da Saúde do Brasil e a Organização Mundial da Saúde tem apoiado a investigação de novas tecnologias que possam contribuir para a vigilância, novos tratamentos e controle da leishmaniose visceral no país. Assim, o objetivo deste trabalho foi isolar compostos de plantas do bioma Caatinga, e investigar a toxicidade destes compostos contra as formas promastigotas e amastigotas de Leishmania infantum chagasi, principal parasita responsável pela leishmaniose visceral na América do Sul, e avaliar a sua capacidade para inibir a enzima acetil-colinesterase (AChE). Após a exposição aos compostos em estudo, foram realizados testes utilizando a forma promastigota que expressa luciferase e ELISA in situ para medir a viabilidade das formas promastigotas e amastigota, respectivamente. O ensaio colorimétrico MTT foi realizado para determinar a toxicidade destas substâncias utilizando células monocíticas murina RAW 264.7. Todos os compostos foram testados in vitro para as sua propriedade anti-colinesterásica. Um cumarina, escoparona, foi isolada a partir de hastes de Platymiscium floribundum, e os flavonóides, rutina e quercetina, foram isolados a partir de grãos de Dimorphandra gardneriana. Estes compostos foram purificados, utilizando cromatografia em coluna gel eluída com solventes orgânicos em misturas de polaridade crescente, e identificados por análise espectral. Nos ensaios leishmanicidas, os compostos fenólicos mostraram eficácia contra as formas extracelulares promastigotas, com EC50 para escoporona de 21.4µg/mL e para quercetina e rutina 26 e 30.3µg/mL, respectivamente. Os flavonóides apresentaram resultados comparáveis à droga controle, a anfotericina B, contra as formas amastigotas com EC50 para quercetina e rutina de 10.6 e 43.3µg/mL, respectivamente. Os compostos inibiram a enzima AChE com halos de inibição variando de 0,8 a 0,6cm, indicando um possível mecanismo de ação para a atividade leishmanicida.