A cyclopalladated complex interacts with mitochondrial membrane thiol-groups and induces the apoptotic intrinsic pathway in murine and cisplatin-resistant human tumor cells

<p>Abstract</p> <p>Background</p> <p>Systemic therapy for cancer metastatic lesions is difficult and generally renders a poor clinical response. Structural analogs of cisplatin, the most widely used synthetic metal complexes, show toxic side-effects and tumor cell resistance. Recently, palladium complexes with increased stability are being investigated to circumvent these limitations, and a biphosphinic cyclopalladated complex {Pd₂[<it>S_(-)</it>C², N-dmpa]₂(μ-dppe)Cl₂} named C7a efficiently controls the subcutaneous development of B16F10-Nex2 murine melanoma in syngeneic mice. Presently, we investigated the melanoma cell killing mechanism induced by C7a, and extended preclinical studies.</p> <p>Methods</p> <p>B16F10-Nex2 cells were treated <it>in vitro </it>with C7a in the presence/absence of DTT, and several parameters related to apoptosis induction were evaluated. Preclinical studies were performed, and mice were endovenously inoculated with B16F10-Nex2 cells, intraperitoneally treated with C7a, and lung metastatic nodules were counted. The cytotoxic effects and the respiratory metabolism were also determined in human tumor cell lines treated <it>in vitro </it>with C7a.</p> <p>Results</p> <p>Cyclopalladated complex interacts with thiol groups on the mitochondrial membrane proteins, causes dissipation of the mitochondrial membrane potential, and induces Bax translocation from the cytosol to mitochondria, colocalizing with a mitochondrial tracker. C7a also induced an increase in cytosolic calcium concentration, mainly from intracellular compartments, and a significant decrease in the ATP levels. Activation of effector caspases, chromatin condensation and DNA degradation, suggested that C7a activates the apoptotic intrinsic pathway in murine melanoma cells. In the preclinical studies, the C7a complex protected against murine metastatic melanoma and induced death in several human tumor cell lineages <it>in vitro</it>, including cisplatin-resistant ones. The mitochondria-dependent cell death was also induced by C7a in human tumor cells.</p> <p>Conclusions</p> <p>The cyclopalladated C7a complex is an effective chemotherapeutic anticancer compound against primary and metastatic murine and human tumors, including cisplatin-resistant cells, inducing apoptotic cell death via the intrinsic pathway.</p

Isolamento e avaliação do potencial citotóxico de derivados fenólicos de Schinus terebinthifolius Raddi (Anacardiaceae)

The EtOH extract from leaves of S. terebinthifolius was subjected to partition between EtOH:H2O and hexane, CH2Cl2, and EtOAc. The phases obtained were evaluated in vitro against human tumoral cell lines and the EtOAc phase exhibited activity. Chromatographic procedures afforded gallic acid (1), methyl (2) and ethyl (3) gallates, trans-catechin (4), quercitrin (5), and afzelin (6), being the first occurrence of 1, 4 and 6 in S. terebinthifolius.In vitro cytotoxic evaluation of 1 - 6 indicated that gallic acid (1) displayed higher activity than ethyl gallate (3) against HL-60 and HeLa cells, while compounds 2, 4 - 6 were inactive

Análise de mobilidade entre Cidades Gêmeas: uma abordagem por Lógica Difusa

Esta pesquisa busca analisar o translado entre três grupos de Cidades Gêmeas e através de técnicas de Simulação Computacional e lógica difusa, traduzir um conjunto de entradas linguísticas em pareceres acerca da mobilidade urbana. Deste modo, o objetivo geral desta pesquisa consiste em identificar um conjunto de recomendações para o trânsito entre as cidades de Itajaí e Navegantes. Como critério de análise foram investigados o comportamento de Cidades Gêmeas, separadas por mar ou rio e com concentrações de fluxo semelhantes. Foram investigados o comportamento de dois pares de cidades Brasileiras Itajaí/Navegantes e Florianópolis/São José, além de um terceiro par de cidades: Cambridge/Boston. Com isso foram extraídos dados de eficiência de trânsito, originalmente apresentados como entradas linguísticas de uma rota rápida e uma rota lenta em horários prédeterminados para cada um dos três pares, além disso, foram considerados os custos para o percurso destas rotas considerando o automóvel Onix (mais vendido no Brasil em 2016). Dentre os resultados obtidos se comprovou que as cidades Itajaí/Navegantes, a rota que utiliza o ferry boat, por mais que seja muito mais rápida que a rota alternativa, é menos recomendável, pois o custo de utilização do ferry boat é muito caro. Verifica-se que o uso de uma travessia entre as cidades livre, como é feito nas outras cidades gêmeas, é necessário.

Essential oil of Lippia sidoides and its major compound thymol: toxicity and walking response of populations of Sitophilus zeamais (Coleoptera: Curculionidae)

The maize weevil, Sitophilus zeamais (Motschulsky) (Coleoptera: Curculionidae), is the main pest of stored grains across tropical regions. An alternative strategy to the use of synthetic insecticides for the management of S. zeamais is the development of botanical insecticides based in the essential oils (EOs) from aromatic plants. In the present study, we evaluated the lethal and sublethal effects of the EO of Lippia sidoides (Cham.) and its major compounds (thymol and ρ-cymene) on different populations of S. zeamais. For this, we determined toxicity by fumigation of treatments of five populations from different Brazilian regions and assessed the lethal time and walking behavior for the most tolerant and susceptible populations. The lethal concentration required to kill 50% of S. zeamais populations ranged from 35.48 to 118.29 μL L^−1 air for EO of L. sidoides, 65.00–91.23 μL L^−1 air for thymol and 801.24 to 2188,83 μL L^−1 air for ρ-cymene. Population from Jacarezinho was the most tolerant to treatments, while population of Rio Branco was the most susceptible one. The survival of S. zeamais populations was significantly affected by treatments and ρ-cymene showed the faster action on both Jacarezinho and Rio Branco populations (LT50 = 0.3 h). The walking behavior of maize weevil showed that the EO of L. sidoides and thymol present repellent effect, however, ρ-cymene present attractive effect. Therefore, the EO of L. sidoides and its major compound thymol are promising source to develop bioinsecticides for the management of S. zeamais populations with different levels of resistance

Morpho-agronomic characterization of sweet potato germplasm

<div><p>ABSTRACT Sweet potato (Ipomoea batatas) spreads mainly by vegetative propagation, and therefore this vegetable may have duplicate accessions in germplasm banks. The authors aimed to characterize morpho-agronomically the sweet potato germplasm from the Active Germplasm Bank (AGB) of Universidade Federal de Sergipe (UFS).The experiment was carried out at the Research Farm “Campus Rural da UFS”. The experimental design was a randomized block design, testing 73 sweet potato accessions with two replicates and four plants per plot. Morpho-agronomic traits of aboveground part and roots were evaluated. We observed that the leaf lobe type, the number of lobes per leaf, shape of central lobe, and general leaf shape were traits which provided the most variability among the accessions. For damage caused by soil insects, 52 accessions showed tolerance. The accessions presented a range from 0.33 to 2.71 t/ha for dry mass of aboveground part and from 1.20 to 10.89 t/ha for the total productivity of the roots. The high phenotypic variability of this crop shows good prospect for breeding programs.</p></div