Kaurene diterpene induces apoptosis in U87 human malignant glioblastoma cells by suppression of anti-apoptotic signals and activation of cysteine proteases

Gliomas are the most common and malignant primary brain tumors in humans. Studies have shown that classes of kaurene diterpene have anti-tumor activity related to their ability to induce apoptosis. We investigated the response of the human glioblastoma cell line U87 to treatment with ent-kaur-16-en-19-oic acid (kaurenoic acid, KA). We analyzed cell survival and the induction of apoptosis using flow cytometry and annexin V staining. Additionally, the expression of anti-apoptotic (c-FLIP and miR-21) and apoptotic (Fas, caspase-3 and caspase-8) genes was analyzed by relative quantification (real-time PCR) of mRNA levels in U87 cells that were either untreated or treated with KA (30, 50, or 70 µM) for 24, 48, and 72 h. U87 cells treated with KA demonstrated reduced viability, and an increase in annexin V- and annexin V/PI-positive cells was observed. The percentage of apoptotic cells was 9% for control cells, 26% for cells submitted to 48 h of treatment with 50 µM KA, and 31% for cells submitted to 48 h of treatment with 70 µM KA. Similarly, in U87 cells treated with KA for 48 h, we observed an increase in the expression of apoptotic genes (caspase-8, -3) and a decrease in the expression of anti-apoptotic genes (miR-21 and c-FLIP). KA possesses several interesting properties and induces apoptosis through a unique mechanism. Further experiments will be necessary to determine if KA may be used as a lead compound for the development of new chemotherapeutic drugs for the treatment of primary brain tumors.

Tumor primário de pulmão simulando doença de Alzheimer: relato de caso

RESUMO Retratamos o relato de um homem de 61 anos que apresentava um glioblastoma multiforme em região do giro têmporo-occipital lateral esquerdo que rechaça cranialmente o hipocampo e o corno temporal do ventrículo lateral correspondente. Não havia sinais e sintomas neurológicos e o quadro clínico lembrava a demência de Alzheimer. Havia comprometimento de memória e alterações comportamentais com duração de três meses. Foram afastadas inicialmente outras causas de demência rapidamente progressivas e a ressonância magnética revelou a etiologia tumoral dos sintomas neuropsiquiátricos. Foi submetido à bateria de testes neuropsicométricos com pontuação compatível com doença de Alzheimer (DA). Em razão de extensa área de edema, foi introduzida dexametasona com reversão completa dos sintomas neuropsiquiátricos iniciais e a repetição da bateria neuropsicológica mostrou melhora acentuada em todos os testes. Optou-se por tratamento conservador, após biópsia por agulha, com evolução para óbito em cinco meses.

Comparative dosimetry in intracavitary balloon catheter brachytherapy with I-125 and in Cf-252 brachytherapy combined with BNCT for brain tumors

Objective Comparative analysis of dosimetry in intracavitary balloon catheter brachytherapy with I-125 and in Cf-252 brachytherapy combined with BNCT for treatment of brain tumors. Materials and Methods Simulations of intracavitary balloon catheter brachytherapy with I-125 and in Cf-252 brachytherapy combined with BNCT were performed with the MCNP5 code, modeling the treatment of a brain tumor on a voxel computational phantom representing a human head. Absorbed dose rates were converted into biologically weighted dose rates. Results Intracavitary balloon catheter brachytherapy with I-125 produced biologically weighted mean dose rates of 3.2E-11, 1.3E-10, 1.9E-11 and 6.9E-13 RBE.Gy.h-1.p-1.s, respectively, on the healthy tissue, on the balloon periphery and on the I 1 and I 2 tumor infiltration zones. On the other hand, Cf-252 brachytherapy combined with BNCT produced a biologically weighted mean dose rate of 5.2E-09, 2.3E-07, 8.7E-09 and 2.4E-09 RBE.Gy.h-1.p-1.s, respectively on the healthy tissue, on the target tumor and on the I 1 and I 2 infiltration zones. Conclusion Cf-252 brachytherapy combined with BNCT delivered a selective irradiation to the target tumor and to infiltration zones, while intracavitary balloon catheter brachytherapy with I-125 delivered negligible doses on the tumor infiltration zones.

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.