Xylodiol from Xylopia langsdorfiana induces apoptosis in HL60 cells

An atisane diterpene was isolated from Xylopia langsdorfiana St. Hilaire & Tulasne, Annonaceae, leaves, ent-atisane-7α,16α-diol (xylodiol). Preliminary study showed that xylodiol was cytotoxic and induced differentiation on human leukemia cell lines. However, the molecular mechanisms of xylodiol-mediated cytotoxicity have not been fully defined. Thus, we investigated the anti-tumor effect of xylodiol in human leukemia HL60 cell line. Xylodiol induced apoptosis and necrosis. HL60 cells treated with xylodiol showed biochemical changes characteristic of apoptosis, including caspases-8, -9 and -3 activation and loss of mitochondrial transmembrane potential (∆ Ψm). However, there was a condensation rather than swelling of mitochondria. Moreover, the formation of condensed mitochondria and the loss of ∆ Ψm occurred downstream of caspase activation. Cyclosporine A did not protect HL60 cells from the cytotoxic effects of xylodiol, suggesting that the loss of ∆ Ψm is a late event in xylodiol-induced apoptosis. Oxidative stress was involved in xylodiol-induced apoptosis. Thus, we conclude that activated caspases cleave cellular proteins resulting in mitochondrial damage leading to mitochondrial condensation, loss of ∆ Ψm and ROS release from the mitochondria. ROS can further induce and maintain a collapse of ∆ Ψm leading to cellular damage through oxidation of lipids and proteins resulting in apoptotic cell death.

Effect of angiotensin II and losartan on the phagocytic activity of peritoneal macrophages from Balb/C mice

Angiotensin II (AII), a product of rennin-angiotensin system, exerts an important role on the function of immune system cells. In this study, the effect of AII on the phagocytic activity of mouse peritoneal macrophages was assessed. Mice peritoneal macrophages were cultured for 48 h and the influence of different concentrations of AII (10-14 to 10-7 M) and/or losartan, 10-16 to 10-6 M), an AT1 angiotensin receptor antagonist, on phagocytic activity and superoxide anion production was determined. Dimethylthiazoldiphenyltetrazolium bromide reduction and the nucleic acid content were used to assess the cytotoxicity of losartan. A stimulatory effect on phagocytic activity (P < 0.05) was observed with 10-13 M and 10-12 M AII concentrations. The addition of losartan (up to10-14 M) to the cell cultures blocked (P < 0.001) the phagocytosis indicating the involvement of AT1 receptors. In contrast, superoxide anion production was not affected by AII or losartan. The existence of AT1 and AT2 receptors in peritoneal macrophages was demonstrated by immunofluorescence microscopy. These results support the hypothesis that AII receptors can modulate murine macrophage activity and phagocytosis, and suggest that AII may have a therapeutic role as an immunomodulatory agent in modifying the host resistance to infection.

Citotoxicidade do promotor de tumor e sua ação mitogênica sobre os linfócitos humanos / Cytotoxicity studies of okadaic acid on human lymphocytes and its mitogenic effect

Proteínas fosfatases são moléculas sinalizadoras que agem juntamente com as proteínas quinases para regular uma variedade de processos celulares fundamentais, bem como, crescimento celular, mitogênese, metabolismo, transcrição de gene, ciclo celular e resposta ao estresse e imune. O ácido okadáico é um potente e específico inibidor de proteína serina/treonina fosfatase (PP1 e PP2A). O objetivo deste estudo foi avaliar o efeito citotóxico do ácido okadáico na viabilidade de linfócitos humanos e sua ação mitogênica. Nos estudos de citotoxicidade avaliamos o efeito do ácido okadáico através dos seguintes parâmetros: redução do MTT (integridade mitocondrial), conteúdo total de proteínas (número de células) e atividade fosfatásica (metabolismo celular). O valor para redução do MTT e atividade fosfatase foram: 50nM e 100nM, respectivamente; não foi encontrado valor de IC50 para o conteúdo de proteína. A atividade fosfatásica não foi afetada pelo ácido okadáico (100nM) quando este composto foi adicionado no extrato celular. A proliferação de linfócitos foi estimulada em 25 porcento quando as células foram tratadas com o ácido okadáico durante o plaqueamento e na ausência da fitohemaglutinina (mitogêno). O estímulo máximo foi até 30 minutos. O ácido okadáico não foi citotóxico para os linfócitos. A ação mitogênica deste composto foi confirmada pelo conteúdo de proteína.

O magnésio e o sistema biológico / Magnesium and the biological system

Desde que o magnésio foi introduzido na terapia há aproximadamente 30 anos, inúmeros estudos clínicos deveriam ter sido feitos. Embora um grande número de resultados experimentais tem demonstrado a importância do magnésio em eventos biológicos, o interesse pela terapia com magnésio ainda caminha a passos lentos, podendo ser atribuído principalmente às restriçöes dirigidas à prevençäo de doenças, particularmente aquelas associadas ao sistema imune. Entretanto, as aplicaçöes promissoras da terapia com magnésio vêm progredindo à luz da dedicaçäo de grupos de pesquisa de excelência, fazendo que a significância do magnésio näo seja ignorada. O propósito deste trabalho é o de resumir alguns aspectos relevantes da importância biológica deste cátion, com especial atençäo ao seu papel nos mecanismos de resistência e imunocompetência.

Bacterial chemistry. VI. Biological activities and cytotoxicity of 1, 3-dihydro-2H-indol-2-one derivatives

The biosynthetic pigment from Chromobacterium violaceum BB-78, 1,3-dihydro-2H-indol-2-one and its derivatives exhibit biological activities such as antimicrobial action, low hemolytic effects on red blood cells and in vitro trypanocide activity. A relatively high cytotoxicity on V-79 hamster fibroblast cells of the biosynthetic pigment was found, although with the methylol derivative the toxicity was almost eliminated. The methylol derivative exhibited similar toxicity as Nifurtimox, a known, commercial trypanocide compound

Bacterial chemistry-III: preliminary studies on Trypanosomal activities of Chromobacterium violaceum products

It has been found that the pigment-I from Chromobacterium violaceum, 3 [1,2 dihydro 5 (5 hydroxy 1H indol 3 yl) 2 oxo 3H pyrrol-3 ylidiene] 1,3 dihydro 2H indol 2 one, has trypanocide activity. The formylated derivatives, pigment-III, immobilized 100% of the Trypanosoma cruzi at a level of 46 micronM after 48h of interaction with a total growth inhibition in the same period. Pigment I exhibited low toxicity and a DNA synthesis inhibition similar to that of Nifurtimox, a known trypanocide compound

Bacterial chemistry - IV. Complete characterization of violacein: an antibiotic and trypanocide pigment from chromobacterium violaceum

Chromobacterium violaceum, Brazilian or Chilean strain, produces a pigment 3 [1,2-dihydro-5 (5-hydroxy-JH-indo) 2-oxo-3H-pyrrol-3-ylidene] 1,3-dihydro-2H-indol-2-one (Violacein). Violacein was isolated from acetone extract in both cases and identified by ultraviolet-visible., infrared, nuclear magnetic rosonance spectroscopy and by mass spectrometry. A derivative of violacein, the tetracetyl-violacein was synthetized in order to confirm the violacein structure. The biosynthesis of C=violacein is also reported