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[PMID]: 28866054 [Au] Autor: Dalla S; Baum M; Dobler S [Ad] Endereço: Institute of Zoology, Universität Hamburg, Martin-Luther-King Pl. 3, 20146 Hamburg, Germany. [Ti] Título: Substitutions in the cardenolide binding site and interaction of subunits affect kinetics besides cardenolide sensitivity of insect Na,K-ATPase. [So] Source: Insect Biochem Mol Biol;89:43-50, 2017 Oct. [Is] ISSN: 1879-0240 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: Substitutions within the cardenolide target site of several insects' Na,K-ATPase α-subunits may confer resistance against toxic cardenolides. However, to which extent these substitutions alter the Na,K-ATPase's kinetic properties and how they interact with different ß-subunits is not clear. The cardenolide-adapted milkweed bug Oncopeltus fasciatus possesses three paralogs of the α-subunit (A, B, and C) that differ in number and identity of resistance-conferring substitutions. We introduced these substitutions into the α-subunit of Drosophila melanogaster and combined them with the ß-subunits Nrv2.2 and Nrv3. The substitutions Q111T-N122H-F786N-T797A (A-copy mimic) and Q111T-N122H-F786N (B-copy mimic) mediated high insensitivity to ouabain, yet they drastically lowered ATPase activity. Remarkably, the identity of the ß-subunit was decisive and all α-subunits were less active when combined with Nrv3 than when combined with Nrv2.2. Both the substitutions and the co-expressed ß-subunit strongly affected the enyzme's affinity for Na and K . Na affinity was considerably higher for all enzymes expressed with nrv3 while expression with nrv2.2 mostly increased K affinity. Our results provide the first evidence that resistance against cardenolides comes at the cost of significantly altered kinetic properties of the Na,K-ATPase. The ß-subunit can strongly modulate these properties but cannot fully compensate for the effect of the substitutions. [Mh] Termos MeSH primário: Cardenolídeos/metabolismo Hemípteros/enzimologia ATPase Trocadora de Sódio-Potássio/metabolismo [Mh] Termos MeSH secundário: Substituição de Aminoácidos Animais Linhagem Celular Drosophila melanogaster Proteínas de Insetos/metabolismo Ouabaína [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Cardenolides); 0 (Insect Proteins); 5ACL011P69 (Ouabain); EC 3.6.3.9 (Sodium-Potassium-Exchanging ATPase) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171024 [Lr] Data última revisão: 171024 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170904 [St] Status: MEDLINE

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[PMID]: 28598616 [Au] Autor: Kaneta Y; Arai MA; Ishikawa N; Toume K; Koyano T; Kowithayakorn T; Chiba T; Iwama A; Ishibashi M [Ad] Endereço: Graduate School of Pharmaceutical Sciences, Chiba University , 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan. [Ti] Título: Identification of BMI1 Promoter Inhibitors from Beaumontia murtonii and Eugenia operculata. [So] Source: J Nat Prod;80(6):1853-1859, 2017 Jun 23. [Is] ISSN: 1520-6025 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: B-Cell-specific Moloney murine leukemia virus insertion region 1 (BMI1) is a core component of the polycomb repressive complex 1 (PRC1). Abnormal expression of BMI1 is associated with a number of human malignances and cancer stem cells (CSCs), which cause chemotherapy resistance. Therefore, small molecules that inhibit BMI1 expression are potential candidates for cancer therapy. In this study, a cell-based reporter gene assay was developed that allowed BMI1 promoter activity to be measured in 293T human embryonic kidney cells based on luciferase expression levels. Using this screening assay, the methanol-soluble extracts of Beaumontia murtonii and Eugenia operculata were selected as leads. Bioassay-guided fractionation of the extracts led to the isolation of three known cardenolides (1-3) and one new compound (4) from B. murtonii and two known triterpenoids (5 and 6) and one new compound (7) from E. operculata. These seven compounds inhibited BMI1 promoter activity (IC range 0.093-23.0 µM), and the most active compound, wallichoside (1), was further evaluated. Western blot analysis revealed that wallichoside (1) decreases BMI1 protein levels in HCT116 human colon carcinoma cells, and flow cytometry analysis showed that it significantly reduced levels of the CSC biomarker epithelial cell adhesion molecule. Wallichoside (1) also inhibited sphere formation of Huh7 human hepatocellular carcinoma cells, indicating that it diminished the self-renewal capability of CSCs. [Mh] Termos MeSH primário: Apocynaceae/química Eugenia/química Complexo Repressor Polycomb 1/metabolismo [Mh] Termos MeSH secundário: Animais Antineoplásicos/química Antineoplásicos/isolamento & purificação Antineoplásicos/farmacologia Western Blotting Carcinoma Hepatocelular/tratamento farmacológico Cardenolídeos/química Cardenolídeos/isolamento & purificação Cardenolídeos/farmacologia Linhagem Celular Tumoral Células HCT116 Células HEK293 Seres Humanos Concentração Inibidora 50 Neoplasias Hepáticas/tratamento farmacológico Camundongos Estrutura Molecular Células-Tronco Neoplásicas/efeitos dos fármacos Folhas de Planta/química Tailândia Triterpenos/química Triterpenos/isolamento & purificação Triterpenos/farmacologia [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antineoplastic Agents); 0 (BMI1 protein, human); 0 (Cardenolides); 0 (Triterpenes); EC 2.3.2.27 (Polycomb Repressive Complex 1) [Em] Mês de entrada: 1708 [Cu] Atualização por classe: 170830 [Lr] Data última revisão: 170830 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170610 [St] Status: MEDLINE [do] DOI: 10.1021/acs.jnatprod.7b00138

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[PMID]: 28597038 [Au] Autor: Pan L; Zhang Y; Zhao W; Zhou X; Wang C; Deng F [Ad] Endereço: Department of Pharmacy, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, 510515, China. [Ti] Título: The cardiac glycoside oleandrin induces apoptosis in human colon cancer cells via the mitochondrial pathway. [So] Source: Cancer Chemother Pharmacol;80(1):91-100, 2017 Jul. [Is] ISSN: 1432-0843 [Cp] País de publicação: Germany [La] Idioma: eng [Ab] Resumo: PURPOSE: Evidence indicates that the cardiac glycoside oleandrin exhibits cytotoxic activity against several different types of cancer. However, the specific mechanisms underlying oleandrin-induced anti-tumor effects remain largely unknown. The present study examined the anti-cancer effect and underlying mechanism of oleandrin on human colon cancer cells. METHODS: The cytotoxicity and IC50 of five small molecule compounds (oleandrin, neriifolin, strophanthidin, gitoxigenin, and convallatoxin) in human colon cancer cell line SW480 cells and normal human colon cell line NCM460 cells were determined by cell counting and MTT assays, respectively. Apoptosis was determined by staining cells with annexin V-FITC and propidium iodide, followed by flow cytometry. Intracellular Ca was determined using Fluo-3 AM,glutathione (GSH) levels were measured using a GSH detection kit,and the activity of caspase-3, -9 was measured using a peptide substrate. BAX, pro-caspase-3, -9, cytochrome C and BCL-2 expression were determined by Western blotting. RESULTS: Oleandrin significantly decreased cell viabilities in SW480, HCT116 and RKO cells. The IC50 for SW480 cells was 0.02 µM, whereas for NCM460 cells 0.56 µM. More interestingly, the results of flow cytometry showed that oleandrin potently induced apoptosis in SW480 and RKO cells. Oleandrin downregulated protein expression of pro-caspase-3, -9, but enhanced caspase-3, -9 activities. These effects were accompanied by upregulation of protein expression of cytochrome C and BAX, and downregulation of BCL-2 protein expression in a concentration-dependent manner. Furthermore, oleandrin increased intracellular Ca concentration, but decreased GSH concentration in the cells. CONCLUSIONS: The present results suggest that oleandrin induces apoptosis in human colorectal cancer cells via the mitochondrial pathway. Our findings provide new insight into the mechanism of anti-cancer property of oleandrin. [Mh] Termos MeSH primário: Antineoplásicos Fitogênicos/farmacologia Apoptose/efeitos dos fármacos Cardenolídeos/farmacologia Neoplasias do Colo/tratamento farmacológico Mitocôndrias/efeitos dos fármacos [Mh] Termos MeSH secundário: Antineoplásicos Fitogênicos/administração & dosagem Cálcio/metabolismo Cardenolídeos/administração & dosagem Caspase 3/metabolismo Caspase 9/metabolismo Linhagem Celular Linhagem Celular Tumoral Colo/citologia Colo/efeitos dos fármacos Neoplasias do Colo/patologia Relação Dose-Resposta a Droga Regulação para Baixo/efeitos dos fármacos Citometria de Fluxo Glutationa/metabolismo Seres Humanos Concentração Inibidora 50 Mitocôndrias/metabolismo Regulação para Cima/efeitos dos fármacos [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antineoplastic Agents, Phytogenic); 0 (Cardenolides); EC 3.4.22.- (Caspase 3); EC 3.4.22.- (Caspase 9); GAN16C9B8O (Glutathione); II95UDU7I4 (oleandrin); SY7Q814VUP (Calcium) [Em] Mês de entrada: 1707 [Cu] Atualização por classe: 170717 [Lr] Data última revisão: 170717 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170610 [St] Status: MEDLINE [do] DOI: 10.1007/s00280-017-3337-2

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[PMID]: 28438630 [Au] Autor: Yang CW; Chang HY; Hsu HY; Lee YZ; Chang HS; Chen IS; Lee SJ [Ad] Endereço: Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli 35053, Taiwan, ROC. [Ti] Título: Identification of anti-viral activity of the cardenolides, Na /K -ATPase inhibitors, against porcine transmissible gastroenteritis virus. [So] Source: Toxicol Appl Pharmacol;332:129-137, 2017 Oct 01. [Is] ISSN: 1096-0333 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: A series of naturally occurring cardenolides that exhibit potent anti-transmissible gastroenteritis virus (TGEV) activity in swine testicular (ST) cells has been identified. In an immunofluorescence assay, these cardenolides were found to diminish the expressions of TGEV nucleocapsid and spike protein, which was used as an indication for viral replication; block TGEV infection induced apoptosis and cytopathic effects; and impart the same trend of inhibitory activity against Na /K -ATPase as for anti-TGEV activity. The viral titer inhibition was found to take place in a dose-dependent manner. Knocking down expression of Na /K -ATPase, the cellular receptor of cardenolides, in ST cells was found to significantly impair the susceptibility of ST cells to TGEV infectivity. Thus, we have identified Na /K -ATPase as an anti-viral drug target and its antagonists, cardenolides, a novel class of anti- TGEV agents. [Mh] Termos MeSH primário: Antivirais/farmacologia Cardenolídeos/farmacologia ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores Vírus da Gastroenterite Transmissível/efeitos dos fármacos [Mh] Termos MeSH secundário: Animais Anticorpos Monoclonais/farmacologia Apoptose/efeitos dos fármacos Relação Dose-Resposta a Droga Células Epiteliais/efeitos dos fármacos Células Epiteliais/metabolismo Inativação Gênica Proteínas do Nucleocapsídeo/genética Proteínas do Nucleocapsídeo/metabolismo RNA Viral/isolamento & purificação ATPase Trocadora de Sódio-Potássio/metabolismo Suínos Vírus da Gastroenterite Transmissível/fisiologia Replicação Viral [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antibodies, Monoclonal); 0 (Antiviral Agents); 0 (Cardenolides); 0 (Nucleocapsid Proteins); 0 (RNA, Viral); EC 3.6.3.9 (Sodium-Potassium-Exchanging ATPase) [Em] Mês de entrada: 1709 [Cu] Atualização por classe: 170925 [Lr] Data última revisão: 170925 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170426 [St] Status: MEDLINE

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[PMID]: 28378871 [Au] Autor: Michalak M; Michalak K; Wicha J [Ad] Endereço: Institute of Organic Chemistry, Polish Academy of Sciences, ul. Marcina Kasprzaka 44/52, 01-224 Warsaw, Poland. jerzy.wicha@icho.edu.pl. [Ti] Título: The synthesis of cardenolide and bufadienolide aglycones, and related steroids bearing a heterocyclic subunit. [So] Source: Nat Prod Rep;34(4):361-410, 2017 Apr 01. [Is] ISSN: 1460-4752 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: Covering: early studies through to March 2016Cardenolides and bufadienolides constitute an attractive class of biologically active steroid derivatives which have been used for the treatment of heart disease in traditional remedies as well as in modern medicinal therapy. Due to their application as therapeutic agents and their unique molecular structures, bearing unsaturated 5- or 6-membered lactones (or other heterocycles) attached to the steroid core, cardio-active steroids have received great attention, which has intensified during the last decade, in the synthetic organic community. Advances in the field of cross-coupling reactions have provided a powerful tool for the attachment of lactone subunits to the steroid core. This current review covers a methodological analysis of synthetic efforts to cardenolide and bufadienolide aglycones. Special emphasis is given to cross-coupling reactions applied for the attachment of lactone subunits at sterically very hindered positions of the steroid core. The carefully selected partial and total syntheses of representative cardio-active steroids will also be presented to exemplify recent achievements (improvements) in the field. [Mh] Termos MeSH primário: Bufanolídeos/síntese química Cardenolídeos/síntese química Esteroides/síntese química [Mh] Termos MeSH secundário: Bufanolídeos/química Cardenolídeos/química Estrutura Molecular Esteroides/química [Pt] Tipo de publicação: JOURNAL ARTICLE; REVIEW [Nm] Nome de substância: 0 (Bufanolides); 0 (Cardenolides); 0 (Steroids) [Em] Mês de entrada: 1705 [Cu] Atualização por classe: 170524 [Lr] Data última revisão: 170524 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170406 [St] Status: MEDLINE [do] DOI: 10.1039/c6np00107f

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[PMID]: 28347742 [Au] Autor: Mohammadi S; French SS; Neuman-Lee LA; Durham SL; Kojima Y; Mori A; Brodie ED; Savitzky AH [Ad] Endereço: Department of Biology, Utah State University, 5305 Old Main Hill, Logan, UT 84322-5305, United States; Ecology Center, Utah State University, 5205 Old Main Hill, Logan, UT 84322-5205, United States. Electronic address: shab.mohammadi@gmail.com. [Ti] Título: Corticosteroid responses of snakes to toxins from toads (bufadienolides) and plants (cardenolides) reflect differences in dietary specializations. [So] Source: Gen Comp Endocrinol;247:16-25, 2017 Jun 01. [Is] ISSN: 1095-6840 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Toads are chemically defended by cardiotonic steroids known as bufadienolides. Resistance to the acute effects of bufadienolides in snakes that prey on toads is conferred by target-site insensitivity of the toxin's target enzyme, the Na /K -ATPase. Previous studies have focused largely on the molecular mechanisms of resistance but have not investigated the physiological mechanisms or consequences of exposure to the toxins. Adrenal enlargement in snakes often is associated with specialization on a diet of toads. These endocrine glands are partly composed of interrenal tissue, which produces the corticosteroids corticosterone and aldosterone. Corticosterone is the main hormone released in response to stress in reptiles, and aldosterone plays an important role in maintaining ion balance through upregulation of Na /K -ATPase. We tested the endocrine response of select species of snakes to acute cardiotonic steroid exposure by measuring circulating aldosterone and corticosterone concentrations. We found that Rhabdophis tigrinus, which specializes on a diet of toads, responds with lower corticosterone and higher aldosterone compared to other species that exhibit target-site resistance to the toxins but do not specialize on toads. We also found differences between sexes in R. tigrinus, with males generally responding with higher corticosterone and aldosterone than females. This study provides evidence of physiological adaptations, beyond target-site resistance, associated with tolerance of bufadienolides in a specialized toad-eating snake. [Mh] Termos MeSH primário: Bufanolídeos/toxicidade Cardenolídeos/toxicidade Colubridae/fisiologia Corticosterona/metabolismo Dieta [Mh] Termos MeSH secundário: Aldosterona/sangue Animais Comportamento Animal/efeitos dos fármacos Bufanolídeos/química Cardenolídeos/química Colubridae/sangue Feminino Masculino Ouabaína/toxicidade [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Bufanolides); 0 (Cardenolides); 4964P6T9RB (Aldosterone); 5ACL011P69 (Ouabain); W980KJ009P (Corticosterone) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171009 [Lr] Data última revisão: 171009 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170329 [St] Status: MEDLINE

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[PMID]: 28334410 [Au] Autor: Rafter JL; Vendettuoli JF; Gonda-King L; Niesen D; Seeram NP; Rigsby CM; Preisser EL [Ad] Endereço: Department of Biological Sciences, University of Rhode Island, Kingston, RI 02881 ( jamierafter@gmail.com ; jvendettuoli@gmail.com ; lmgondaking@gmail.com ; chad3332@gmail.com ; preisser@uri.edu ). [Ti] Título: Pretty Picky for a Generalist: Impacts of Toxicity and Nutritional Quality on Mantid Prey Processing. [So] Source: Environ Entomol;46(3):626-632, 2017 06 01. [Is] ISSN: 1938-2936 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: Prey have evolved a number of defenses against predation, and predators have developed means of countering these protective measures. Although caterpillars of the monarch butterfly, Danaus plexippus L., are defended by cardenolides sequestered from their host plants, the Chinese mantid Tenodera sinensis Saussure guts the caterpillar before consuming the rest of the body. We hypothesized that this gutting behavior might be driven by the heterogeneous quality of prey tissue with respect to toxicity and/or nutrients. We conducted behavioral trials in which mantids were offered cardenolide-containing and cardenolide-free D. plexippus caterpillars and butterflies. In addition, we fed mantids starved and unstarved D. plexippus caterpillars from each cardenolide treatment and nontoxic Ostrinia nubilalis Hübner caterpillars. These trials were coupled with elemental analysis of the gut and body tissues of both D. plexippus caterpillars and corn borers. Cardenolides did not affect mantid behavior: mantids gutted both cardenolide-containing and cardenolide-free caterpillars. In contrast, mantids consumed both O. nubilalis and starved D. plexippus caterpillars entirely. Danaus plexippus body tissue has a lower C:N ratio than their gut contents, while O. nubilalis have similar ratios; gutting may reflect the mantid's ability to regulate nutrient uptake. Our results suggest that post-capture prey processing by mantids is likely driven by a sophisticated assessment of resource quality. [Mh] Termos MeSH primário: Borboletas/química Cardenolídeos/toxicidade Mantódeos/fisiologia Valor Nutritivo Comportamento Predatório [Mh] Termos MeSH secundário: Animais Larva/química [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Cardenolides) [Em] Mês de entrada: 1707 [Cu] Atualização por classe: 171126 [Lr] Data última revisão: 171126 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170324 [St] Status: MEDLINE [do] DOI: 10.1093/ee/nvx038

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[PMID]: 28323544 [Au] Autor: Hoang K; Tao L; Hunter MD; de Roode JC [Ad] Endereço: Department of Biology, Emory University, 1510 Clifton Road, Atlanta, Georgia 30322. Correspondence should be sent to Kevin Hoang at: kevinmhoang3@gmail.com. [Ti] Título: Host Diet Affects the Morphology of Monarch Butterfly Parasites. [So] Source: J Parasitol;103(3):228-236, 2017 Jun. [Is] ISSN: 1937-2345 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Understanding host-parasite interactions is essential for ecological research, wildlife conservation, and health management. While most studies focus on numerical traits of parasite groups, such as changes in parasite load, less focus is placed on the traits of individual parasites such as parasite size and shape (parasite morphology). Parasite morphology has significant effects on parasite fitness such as initial colonization of hosts, avoidance of host immune defenses, and the availability of resources for parasite replication. As such, understanding factors that affect parasite morphology is important in predicting the consequences of host-parasite interactions. Here, we studied how host diet affected the spore morphology of a protozoan parasite ( Ophryocystis elektroscirrha ), a specialist parasite of the monarch butterfly ( Danaus plexippus ). We found that different host plant species (milkweeds; Asclepias spp.) significantly affected parasite spore size. Previous studies have found that cardenolides, secondary chemicals in host plants of monarchs, can reduce parasite loads and increase the lifespan of infected butterflies. Adding to this benefit of high cardenolide milkweeds, we found that infected monarchs reared on milkweeds of higher cardenolide concentrations yielded smaller parasites, a potentially hidden characteristic of cardenolides that may have important implications for monarch-parasite interactions. [Mh] Termos MeSH primário: Apicomplexa/ultraestrutura Borboletas/parasitologia [Mh] Termos MeSH secundário: Animais Apicomplexa/crescimento & desenvolvimento Asclepias/química Borboletas/fisiologia Cardenolídeos/metabolismo Dieta Feminino Interações Hospedeiro-Parasita Masculino Esporos de Protozoários/ultraestrutura [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Cardenolides) [Em] Mês de entrada: 1706 [Cu] Atualização por classe: 170628 [Lr] Data última revisão: 170628 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170322 [St] Status: MEDLINE [do] DOI: 10.1645/16-142

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[PMID]: 28300580 [Au] Autor: Mebs D; Wunder C; Pogoda W; Toennes SW [Ad] Endereço: Institute of Legal Medicine, University of Frankfurt, Kennedyallee 104, D-60956 Frankfurt, Germany. Electronic address: mebs@em.uni-frankfurt.de. [Ti] Título: Feeding on toxic prey. The praying mantis (Mantodea) as predator of poisonous butterfly and moth (Lepidoptera) caterpillars. [So] Source: Toxicon;131:16-19, 2017 Jun 01. [Is] ISSN: 1879-3150 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: Caterpillars of the monarch butterfly, Danaus plexippus, feed on milkweed plants, Asclepias spp. (Apocynaceae), and sequester their toxic cardenolides aimed at deterring predators. Nevertheless, Chinese praying mantids, Tenodera sinensis, consume these caterpillars after removing the midgut ("gutting") including its plant content. In the present study, monarch caterpillars raised on A. curassavica, and those of the death's-head hawkmoth, Acherontia atropos, raised on Atropa belladonna containing atropine, were fed to mantids, Hierodula membranacea, which removed the gut of both species discarding about 59% of cardenolides and more than 90% of atropine, respectively. The ingestion of these compounds produced no apparent ill effects in the mantids and both were excreted with faeces. On the other hand, when mantids were fed with larvae of two moth species, Amata mogadorensis and Brahmaea certia, raised on non-poisonous host plants, the mantids showed the same gutting behaviour, thereby discarding indigestible plant material. As polar compounds, e.g. cardenolides and atropine, are not absorbed from the mantids midgut and do not pass the gut membrane, this enables the mantids to feed on toxic prey. [Mh] Termos MeSH primário: Borboletas Mantódeos/fisiologia Mariposas Comportamento Predatório [Mh] Termos MeSH secundário: Animais Asclepias/química Cardenolídeos/química Fezes/química Intestinos Larva Plantas Tóxicas/química [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Cardenolides) [Em] Mês de entrada: 1709 [Cu] Atualização por classe: 170928 [Lr] Data última revisão: 170928 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170317 [St] Status: MEDLINE

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[PMID]: 28292827 [Au] Autor: Garofalo S; Grimaldi A; Chece G; Porzia A; Morrone S; Mainiero F; D'Alessandro G; Esposito V; Cortese B; Di Angelantonio S; Trettel F; Limatola C [Ad] Endereço: Department of Physiology and Pharmacology. [Ti] Título: The Glycoside Oleandrin Reduces Glioma Growth with Direct and Indirect Effects on Tumor Cells. [So] Source: J Neurosci;37(14):3926-3939, 2017 Apr 05. [Is] ISSN: 1529-2401 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Oleandrin is a glycoside that inhibits the ubiquitous enzyme Na /K -ATPase. In addition to its known effects on cardiac muscle, recent and evidence highlighted its potential for anticancer properties. Here, we evaluated for the first time the effect of oleandrin on brain tumors. To this aim, mice were transplanted with human or murine glioma and analyzed for tumor progression upon oleandrin treatment. In both systems, oleandrin impaired glioma development, reduced tumor size, and inhibited cell proliferation. We demonstrated that oleandrin does the following: (1) enhances the brain-derived neurotrophic factor (BDNF) level in the brain; (2) reduces both microglia/macrophage infiltration and CD68 immunoreactivity in the tumor mass; (3) decreases astrogliosis in peritumoral area; and (4) reduces glioma cell infiltration in healthy parenchyma. In BDNF-deficient mice (bdnftm1Jae/J) and in glioma cells silenced for TrkB receptor expression, oleandrin was not effective, indicating a crucial role for BDNF in oleandrin's protective and antitumor functions. In addition, we found that oleandrin increases survival of temozolomide-treated mice. These results encourage the development of oleandrin as possible coadjuvant agent in clinical trials of glioma treatment. In this work, we paved the road for a new therapeutic approach for the treatment of brain tumors, demonstrating the potential of using the cardioactive glycoside oleandrin as a coadjuvant drug to standard chemotherapeutics such as temozolomide. In murine models of glioma, we demonstrated that oleandrin significantly increased mouse survival and reduced tumor growth both directly on tumor cells and indirectly by promoting an antitumor brain microenvironment with a key protective role played by the neurotrophin brain-derived neurotrophic factor. [Mh] Termos MeSH primário: Neoplasias Encefálicas/tratamento farmacológico Cardenolídeos/uso terapêutico Glicosídeos Cardíacos/uso terapêutico Glioma/tratamento farmacológico Carga Tumoral/efeitos dos fármacos [Mh] Termos MeSH secundário: Animais Neoplasias Encefálicas/patologia Cardenolídeos/farmacologia Glicosídeos Cardíacos/farmacologia Linhagem Celular Tumoral Sobrevivência Celular/efeitos dos fármacos Sobrevivência Celular/fisiologia Glioma/patologia Seres Humanos Masculino Camundongos Camundongos Endogâmicos C57BL Camundongos SCID Camundongos Transgênicos Carga Tumoral/fisiologia Ensaios Antitumorais Modelo de Xenoenxerto/métodos [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Cardenolides); 0 (Cardiac Glycosides); II95UDU7I4 (oleandrin) [Em] Mês de entrada: 1707 [Cu] Atualização por classe: 170727 [Lr] Data última revisão: 170727 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170316 [St] Status: MEDLINE [do] DOI: 10.1523/JNEUROSCI.2296-16.2017

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