Esterification of p-Coumaric Acid Improves the Control over Melanoma Cell Growth.

Previous studies reported that p-coumaric acid modulates melanoma growth. Because the esterification of p-coumaric acid (p-CA) enhanced its activity as an antimelanogenic agent, we aimed to determine the antitumor potential of two derivatives, the ethyl and butyl esters, against the murine B16-F10 and the human SK-MEL-25 melanoma cells. Cell viability was determined in vitro by the lactate dehydrogenase release and violet crystal absorption assays. The cell proliferation rate and cell cycle behavior were determined by the colony formation assay and flow cytometry analysis. Although p-CA, at the concentration of 1 mM, failed to exert a significant antitumor activity, the ethyl and butyl ester derivatives caused substantial tumor cell death at doses < 1 mM. Despite a reduction in their direct cytotoxicity at minor doses, both products controlled the melanoma growth by arresting the cell cycle at the G0/G1 (B16-F10) or S/G2 (SK-MEL-25). Furthermore, the in vivo experiments showed that the butyl ester derivative suppressed the lung B16-F10 burden, compared to the p-CA-treated mice. Thus, the esterification of p-coumaric acid improved the control over the proliferation of murine and human melanoma cells and can be considered an approach for designing novel anticancer agents.

Quantum-Dot-Based Iron Oxide Nanoparticles Activate the NLRP3 Inflammasome in Murine Bone Marrow-Derived Dendritic Cells.

Inflammasomes are cytosolic complexes composed of a Nod-like receptor, NLR, the adaptor protein, ASC, and a proteolytic enzyme, caspase-1. Inflammasome activation leads to caspase-1 activation and promotes functional maturation of IL-1ß and IL-18, two prototypical inflammatory cytokines. Besides, inflammasome activation leads to pyroptosis, an inflammatory type of cell death. Inflammasomes are vital for the host to cope with foreign pathogens or tissue damage. Herein, we show that quantum-dot-based iron oxide nanoparticles, MNP@QD, trigger NLRP3 inflammasome activation and subsequent release of proinflammatory interleukin IL-1ß by murine bone marrow-derived dendritic cells (BMDCs). This activation is more pronounced if these cells endocytose the nanoparticles before receiving inflammatory stimulation. MNP@QD was characterized by using imaging techniques like transmission electron microscopy, fluorescence microscopy, and atomic force microscopy, as well as physical and spectroscopical techniques such as fluorescence spectroscopy and powder diffraction. These findings may open the possibility of using the composite MNP@QD as both an imaging and a therapeutic tool.

Ethanolic Extract of Senna velutina Roots: Chemical Composition, In Vitro and In Vivo Antitumor Effects, and B16F10-Nex2 Melanoma Cell Death Mechanisms.

Cutaneous melanoma is among the most aggressive types of cancer, and its rate of occurrence increases every year. Current pharmacological treatments for melanoma are not completely effective, requiring the identification of new drugs. As an alternative, plant-derived natural compounds are described as promising sources of new anticancer drugs. In this context, the objectives of this study were to identify the chemical composition of the ethanolic extract of Senna velutina roots (ESVR), to assess its in vitro and in vivo antitumor effects on melanoma cells, and to characterize its mechanisms of action. For these purposes, the chemical constituents were identified by liquid chromatography coupled to high-resolution mass spectrometry. The in vitro activity of the extract was assessed in the B16F10-Nex2 melanoma cell line using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and based on the apoptotic cell count; DNA fragmentation; necrostatin-1 inhibition; intracellular calcium, pan-caspase, and caspase-3 activation; reactive oxygen species (ROS) levels; and cell cycle arrest. The in vivo activity of the extract was assessed in models of tumor volume progression and pulmonary nodule formation in C57Bl/6 mice. The chemical composition results showed that ESVR contains flavonoid derivatives of the catechin, anthraquinone, and piceatannol groups. The extract reduced B16F10-Nex2 cell viability and promoted apoptotic cell death as well as caspase-3 activation, with increased intracellular calcium and ROS levels as well as cell cycle arrest at the sub-G0/G1 phase. In vivo, the tumor volume progression and pulmonary metastasis of ESVR-treated mice decreased over 50%. Combined, these results show that ESVR had in vitro and in vivo antitumor effects, predominantly by apoptosis, thus demonstrating its potential as a therapeutic agent in the treatment of melanoma and other types of cancer.

In vivo and in vitro effect of killed Propionibacterium acnes and its purified soluble polysaccharide on mouse bone marrow stem cells and dendritic cell differentiation.

Among the effects exerted by Propionibacterium acnes, a most relevant one is its capacity to modulate the Th1/Th2 cellular immune response. This effect depends on the induction and activation of antigen presenting cells, mainly dendritic cells (DCs), whose number is increased in the peripheral blood of animals treated with this bacterium. A soluble P. acnes polysaccharide (PS) extract also acts on DCs, modulating a Th1 immune response. These data led us to investigate the role of P. acnes and its soluble PS on murine bone marrow (BM) DCs. Bone marrow cells were analyzed by flow cytometry, showing an increase of stem cells and DCs in P. acnes- or PS-treated animals. Culturing in the presence of granulocyte monocyte colony stimulating factor (GM-CSF) increased the in vitro differentiation and maturation of these cells into BM-derived DCs (CD11c+ and MHC class II+). Maturation of DCs was determined by increased CD80 and CD86 expression, IL-4 and IL-12 production, reduction in phagocytic capacity and increase in the antigen presenting ability to primed or naïve T lymphocytes. These data indicate that P. acnes as well as its PS can modulate BM stem cells, originating mature DCs, which are important mainly at the initial antigen contact.

Antitumor activity of kielmeyera coriacea leaf constituents in experimental melanoma, tested in vitro and in vivo in syngeneic mice.

PURPOSE: The antitumor activity of Kielmeyera coriacea (Clusiaceae), a medicinal plant used in the treatment of parasitic, as well as fungal and bacterial infections by the Brazilian Cerrado population, was investigated. METHODS: A chloroform extract (CE) of K. coriacea was tested in the murine melanoma cell line (B16F10-Nex2) and a panel of human tumor cell lines. Tumor cell migration was determined by the wound-healing assay and the in vivo antitumor activity of CE was investigated in a melanoma cell metastatic model. 1H NMR and GC/MS were used to determine CE chemical composition. RESULTS: We found that CE exhibited strong cytotoxic activity against murine melanoma cells and a panel of human tumor cell lines in vitro. CE also inhibited growth of B16F10-Nex2 cells at sub lethal concentrations, inducing cell cycle arrest at S phase, and inhibition of tumor cell migration. Most importantly, administration of CE significantly reduced the number of melanoma metastatic nodules in vivo. Chemical analysis of CE indicated the presence of the long chain fatty compounds, 1-eicosanol, 1-docosanol, and 2-nonadecanone as main constituents. CONCLUSION: These results indicate that K. coriacea is a promising medicinal plant in cancer therapy exhibiting antitumor activity both in vitro and in vivo against different tumor cell lines.

Resistance to degradation and cellular distribution are important features for the antitumor activity of gomesin.

Many reports have shown that antimicrobial peptides exhibit anticancer abilities. Gomesin (Gm) exhibits potent cytotoxic activity against cancer cells by a membrane pore formation induced after well-orchestrated intracellular mechanisms. In this report, the replacements of the Cys by Ser or Thr, and the use D-amino acids in the Gm structure were done to investigate the importance of the resistance to degradation of the molecule with its cytotoxicity. [Thr(2,6,11,15)]-Gm, and [Ser(2,6,11,15)]-Gm exhibits low cytotoxicity, and low resistance to degradation, and after 24 h are present in localized area near to the membrane. Conversely, the use of D-amino acids in the analogue [D-Thr(2,6,11,15)]-D-Gm confers resistance to degradation, increases its potency, and maintained this peptide spread in the cytosol similarly to what happens with Gm. Replacements of Cys by Thr and Gln by L- or D-Pro ([D-Thr(2,6,11,15), Pro(9)]-D-Gm, and [Thr(2,6,11,15), D-Pro(9)]-Gm), which induced a similar ß-hairpin conformation, also increase their resistance to degradation, and cytotoxicity, but after 24 h they are not present spread in the cytosol, exhibiting lower cytotoxicity in comparison to Gm. Additionally, chloroquine, a lysosomal enzyme inhibitor potentiated the effect of the peptides. Furthermore, the binding and internalization of peptides was determined, but a direct correlation among these factors was not observed. However, cholesterol ablation, which increase fluidity of cellular membrane, also increase cytotoxicity and internalization of peptides. ß-hairpin spatial conformation, and intracellular localization/target, and the capability of entry are important properties of gomesin cytotoxicity.

Forma micetomatóide de infecçäo por Scedosporium apiospermum: registro de um caso / A mycetoma-Like form infection by Scedosporium apiospermum: report of a case

Scedospsorium apiospermum, forma anamorfa ou assexuada de Pseudallescheria boydii, é fungo ubíquo do solo capaz de provocar infecçöes as mais variadas, tais como ceratite, endoftalmite, sinusite, "bolas fúngicas" intracavitárias, processos inflamatórios bronco-alveolares, lesöes subcutâneas simulando esporotricose, eumicetomas, meningoencefalite etc. Em algumas observaçöes os pacientes estäo imunodeprimidos, muitas vezes com processos leucêmicos graves e neutropenia acentuada. Em outros casos, formas invasivas acentuada. Em outros casos, formas invasivas säo registradas em transplantados renais e aidéticos. No presente trabalho os autores registram um caso de forma micematóide de infecçäo por Scedosporium apiospermum em pacientes do sexo masculino - O.M.M., engenheiro, 38 anos, que se referiu na planta do pé, na regiäo do calcâneo direito, enterrando um ferro de aproximadamente 8mm de diâmeto, estando calçado com um tênis, em dezembro de 1986. Em junho de 1987 apareceu na regiäo maleolar interna processo inflamatório com fístula, drenado escasso secreçäo purulenta sem gräos. Exame micológico positivo para Scedosporium apiospermum. Novo exame realizado alguns meses após, com a retirada de um corpo estranho (fragmento de tênis), revelou o mesmo fungo em cultivo puro. Cura completa após a eliminaçäo desse elemento

Inoculaçäo de antígeno contendo a glicoproteína 43kDa do Paracoccidioides brasiliensis em testículo de hamsters / Intratesticular inoculation of Paracoccidioides brasiliensis antigen containing 43kDa glycoprotein in hamsters

Após um período de cinco semanas à inoculaçäo de antígeno (contendo a glicoproteína de peso molecular 43KDa) puro e diluído a 1/100, em testículo de hamsters, bem como o antígeno controle nas mesmas condiçöes, näo foram identificadas quaisquer alteraçöes histopatológicas tanto local como sistêmica, em órgäo do SRE. Este fato permite concluir que, em tais condiçöes de experimentaçäo, a gp 43 parece näo estar vinculada à virulência do Paracoccidioides brasiliensis