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[PMID]: 28669925 [Au] Autor: Yelken BÖ; Balci T; Süslüer SY; Kayabasi Ç; Avci ÇB; Kirmizibayrak PB; Gündüz C [Ad] Endereço: Faculty of Medicine, Department of Medical Biology, Ege University, Bornova, Izmir, Turkey. [Ti] Título: The effect of tomatine on metastasis related matrix metalloproteinase (MMP) activities in breast cancer cell model. [So] Source: Gene;627:408-411, 2017 Sep 05. [Is] ISSN: 1879-0038 [Cp] País de publicação: Netherlands [La] Idioma: eng [Ab] Resumo: Breast cancer is one of the most common malignancies in women and metastasis is the cause of morbidity and mortality in patients. In the development of metastasis, the matrix metalloproteinase (MMP) family has a very important role in tumor development. MMP-2 and MMP-9 work together for extracellular matrix (ECM) cleavage to increase migration. Tomatine is a secondary metabolite that has a natural defense role against plants, fungi, viruses and bacteria that are synthesized from tomato. In addition, tomatine is also known that it breaks down the cell membrane and is a strong inhibitor in human cancer cells. In this study, it was aimed to evaluate the effect of tomatine on cytotoxicity, apoptosis and matrix metalloproteinase inhibition in MCF-7 cell lines. Human breast cancer cell line (MCF-7) was used as a cell line. In MCF-7 cells, the IC dose of tomatine was determined to be 7.07µM. According to the control cells, apoptosis increased 3.4 fold in 48thh. Activation of MMP-2, MMP-9 and MMP-9\NGAL has been shown to decrease significantly in cells treated with tomatine by gelatin zymography compared to the control. As a result, matrix metalloproteinase activity and cell proliferation were suppressed by tomatine and this may provide support in treatment methods. [Mh] Termos MeSH primário: Antineoplásicos/farmacologia Neoplasias da Mama/metabolismo Metaloproteinases da Matriz/genética Tomatina/farmacologia [Mh] Termos MeSH secundário: Apoptose/efeitos dos fármacos Proliferação Celular/efeitos dos fármacos Seres Humanos Células MCF-7 Metaloproteinases da Matriz/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antineoplastic Agents); 31U6547O08 (Tomatine); EC 3.4.24.- (Matrix Metalloproteinases) [Em] Mês de entrada: 1709 [Cu] Atualização por classe: 170920 [Lr] Data última revisão: 170920 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170704 [St] Status: MEDLINE

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[PMID]: 28300624 [Au] Autor: da Silva DC; Andrade PB; Valentão P; Pereira DM [Ad] Endereço: REQUIMTE/LAQV, Laboratório de Farmacognosia, Departamento de Química, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, N° 228, 4050-213 Porto, Portugal. [Ti] Título: Neurotoxicity of the steroidal alkaloids tomatine and tomatidine is RIP1 kinase- and caspase-independent and involves the eIF2α branch of the endoplasmic reticulum. [So] Source: J Steroid Biochem Mol Biol;171:178-186, 2017 Jul. [Is] ISSN: 1879-1220 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: Steroidal alkaloids are a class of natural products that occur in several species of the Solanaceae family. In the case of the tomato plant (Lycopersicon esculentum Mill.), tomatine and its aglycone, tomatidine, are the most representative molecules. These steroidal alkaloids have already shown several potentially useful biological activities, from anticancer to anti-inflammatory or antibacterial. In this work, the toxicity of these molecules in neuronal cells, namely in the neuroblastoma cell line SH-SY5Y, was assessed, emphasis being given to the cellular mechanisms underlying the effects observed. The results show that tomatine/tomatidine-induced cell death is caspase- and RIP1 kinase-independent, as cell death is not prevented by the pan-caspase inhibitor Z-VAD.fmk or by RIP1 inhibitor necrostatin-1. Analysis of Ca levels using the fluorescent probe Fura-2/AM indicates that both tomatine and tomatidine have a marked effect upon Ca homeostasis by increasing cytosolic Ca , an event that might be associated with their effect upon the endoplasmic reticulum. We show that the toxicity of these molecules require the PERK/eIF2α branch of the unfolded protein response, but not the IRE1α branch. Given the role of the endoplasmic reticulum in proteostasis, the ability of these molecules to inhibit the proteasome was also evaluated. Tomatine was able to inhibit the chymotrypsin-like catalytic core of purified human 20S proteasome, as shown by its ability to prevent degradation of the fluorogenic substrate Suc-Leu-Leu-Val-Tyr-AMC, thus suggesting that interference with proteostasis can be responsible for the toxicity of these steroidal alkaloids. This study is relevant as it sheds a light regarding the toxicity of molecules present in one of the most consumed plants worldwide. [Mh] Termos MeSH primário: Retículo Endoplasmático/efeitos dos fármacos Fator de Iniciação 2 em Eucariotos/antagonistas & inibidores Neurônios/efeitos dos fármacos Inibidores de Proteassoma/toxicidade Tomatina/análogos & derivados Tomatina/toxicidade Resposta a Proteínas não Dobradas/efeitos dos fármacos [Mh] Termos MeSH secundário: Apoptose/efeitos dos fármacos Sinalização do Cálcio/efeitos dos fármacos Inibidores de Caspase/farmacologia Caspases/química Caspases/metabolismo Linhagem Celular Tumoral Nucléolo Celular/efeitos dos fármacos Nucléolo Celular/metabolismo Tamanho do Núcleo Celular/efeitos dos fármacos Forma Celular/efeitos dos fármacos Sobrevivência Celular/efeitos dos fármacos Montagem e Desmontagem da Cromatina/efeitos dos fármacos Retículo Endoplasmático/enzimologia Retículo Endoplasmático/metabolismo Estresse do Retículo Endoplasmático/efeitos dos fármacos Fator de Iniciação 2 em Eucariotos/metabolismo Seres Humanos Lycopersicon esculentum/química Neurônios/citologia Neurônios/metabolismo Inibidores de Proteínas Quinases/farmacologia Proteína Serina-Treonina Quinases de Interação com Receptores/antagonistas & inibidores Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo Tomatina/antagonistas & inibidores [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Caspase Inhibitors); 0 (Eukaryotic Initiation Factor-2); 0 (Proteasome Inhibitors); 0 (Protein Kinase Inhibitors); 2B73S48786 (tomatidine); 31U6547O08 (Tomatine); EC 2.7.11.1 (RIPK1 protein, human); EC 2.7.11.1 (Receptor-Interacting Protein Serine-Threonine Kinases); EC 3.4.22.- (Caspases) [Em] Mês de entrada: 1707 [Cu] Atualização por classe: 170718 [Lr] Data última revisão: 170718 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170317 [St] Status: MEDLINE

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[PMID]: 28109774 [Au] Autor: Carere J; Benfield AH; Ollivier M; Liu CJ; Kazan K; Gardiner DM [Ad] Endereço: Commonwealth Scientific and Industrial Research Organization (CSIRO) Agriculture and Food, Queensland Bioscience Precinct, Brisbane, Queensland 4067, Australia. Electronic address: Jason.Carere@Canada.ca. [Ti] Título: A tomatinase-like enzyme acts as a virulence factor in the wheat pathogen Fusarium graminearum. [So] Source: Fungal Genet Biol;100:33-41, 2017 Mar. [Is] ISSN: 1096-0937 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: During their interactions with plants, fungal pathogens employ large numbers of pathogenesis-associated molecules including secreted effectors and enzymes that can degrade various defence compounds. However, in many cases, in planta targets of pathogen-produced enzymes remain unknown. We identified a gene in the wheat pathogen Fusarium graminearum, encoding a putative enzyme that shows 84% sequence identity to FoTom1, a tomatinase produced by the tomato pathogen Fusarium oxysporum f. sp. lycopersici. In F. oxysporum f. sp. lycopersici, FoTom1 is a virulence factor involved in the degradation of tomato defence compound tomatine, a saponin compound. Given that wheat is unknown to produce tomatine, we tested the ability of F. graminearum to degrade tomatine and found that F. graminearum was unable to degrade tomatine in culture. However, FgTom1 degraded tomatine in vitro when heterologously expressed. To determine the possible function of FgTom1 in pathogen virulence, we generated FgTom1 knockout mutants (ΔTom1). ΔTom1 mutants were not different from wild type when grown in culture but showed significant reduction in pathogen virulence in root rot and head blight assays. In an attempt to identify possible in planta targets of FgTom1, the metabolomes of wheat heads infected with wildtype pathogen and ΔTom1 were compared and several peaks differentially abundant between treatments identified. Although the exact identity of these peaks is currently unknown, this result suggested that FgTom1 may have in planta targets in wheat, possibly tomatine-like saponin compounds. Overall, our results presented here show that FgTom1 is a new virulence factor in F. graminearum. [Mh] Termos MeSH primário: Resistência à Doença/genética Fusarium/enzimologia Glicosídeo Hidrolases/metabolismo Triticum/microbiologia [Mh] Termos MeSH secundário: Fusarium/patogenicidade Glicosídeo Hidrolases/genética Doenças das Plantas/genética Doenças das Plantas/microbiologia Raízes de Plantas/metabolismo Raízes de Plantas/microbiologia Tomatina/química Tomatina/metabolismo Fatores de Virulência/química Fatores de Virulência/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Virulence Factors); 31U6547O08 (Tomatine); EC 3.2.1.- (Glycoside Hydrolases); EC 3.2.1.- (tomatinase) [Em] Mês de entrada: 1707 [Cu] Atualização por classe: 170721 [Lr] Data última revisão: 170721 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170123 [St] Status: MEDLINE

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[PMID]: 27934291 [Au] Autor: Liu J; Kanetake S; Wu YH; Tam C; Cheng LW; Land KM; Friedman M [Ad] Endereço: Department of Biological Sciences, University of the Pacific , Stockton, California 95211, United States. [Ti] Título: Antiprotozoal Effects of the Tomato Tetrasaccharide Glycoalkaloid Tomatine and the Aglycone Tomatidine on Mucosal Trichomonads. [So] Source: J Agric Food Chem;64(46):8806-8810, 2016 Nov 23. [Is] ISSN: 1520-5118 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: The present study investigated the inhibitory effects of the commercial tetrasaccharide tomato glycoalkaloid tomatine and the aglycone tomatidine on three mucosal pathogenic protozoa that are reported to infect humans, cattle, and cats, respectively: Trichomonas vaginalis strain G3, Tritrichomonas foetus strain D1, and Tritrichomonas foetus strain C1. A preliminary screen showed that tomatine at 100 µM concentration completely inhibited the growth of all three trichomonads. In contrast, the inhibition of all three pathogens by tomatidine was much lower, suggesting the involvement of the lycotetraose carbohydrate side chain in the mechanism of inhibition. Midpoints of concentration-response sigmoid plots of tomatine on the three strains correspond to IC values, the concentration that inhibits 50% of growth of the pathogenic protozoa. The concentration data were used to calculate the IC values for G3, D1, and C1 of 7.9, 1.9, and 2.2 µM, respectively. The results show an approximately 4-fold variation from the lowest to the highest value (lowest activity). Although the inhibition by tomatine was not as effective as that of the medicinal drug metronidazole, the relatively low IC values for both T. vaginalis and T. foetus indicated tomatine as a possible natural alternative therapeutic for trichomoniasis in humans and food-producing (cattle and pigs) and domestic (cats) animals. Because tomatine has the potential to serve as a new antiprotozoan functional (medical) food, the distribution of this glycoalkaloid in tomatoes and suggestions for further research are discussed. [Mh] Termos MeSH primário: Antiprotozoários/farmacologia Lycopersicon esculentum/química Extratos Vegetais/farmacologia Tomatina/análogos & derivados Tomatina/farmacologia Trichomonadida/efeitos dos fármacos [Mh] Termos MeSH secundário: Animais Antiprotozoários/química Extratos Vegetais/química Tomatina/química Trichomonadida/química [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antiprotozoal Agents); 0 (Plant Extracts); 2B73S48786 (tomatidine); 31U6547O08 (Tomatine) [Em] Mês de entrada: 1706 [Cu] Atualização por classe: 170602 [Lr] Data última revisão: 170602 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 161210 [St] Status: MEDLINE

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[PMID]: 27760443 [Au] Autor: de Groot C; Müller-Goymann CC [Ad] Endereço: Institut für Pharmazeutische Technologie, Technische Universität Braunschweig, Braunschweig, Germany. [Ti] Título: Saponin Interactions with Model Membrane Systems - Langmuir Monolayer Studies, Hemolysis and Formation of ISCOMs. [So] Source: Planta Med;82(18):1496-1512, 2016 Dec. [Is] ISSN: 1439-0221 [Cp] País de publicação: Germany [La] Idioma: eng [Ab] Resumo: Saponins are used in medicine due to their pharmacological and immunological effects. To better understand interactions of saponins with model membranes and natural membranes of, for example, erythrocytes, Langmuir film balance experiments are well established. For most saponins, a strong interaction with cholesterol was demonstrated in dependence of both the aglycone part and the sugar moieties and is suggested to be correlated with a strong hemolytic activity, high toxicity, and high surface activity, as was demonstrated for the steroid saponin digitonin. In general, changes in the sugar chain or in substituents of the aglycone result in a modification of the saponin properties. A promising saponin with regard to fairly low hemolytic activity and high adjuvant effect is -tomatine, which still shows a high affinity for cholesterol. An interaction with cholesterol and lipids has also been proven for the Quillaja saponin from the bark of Molina. This triterpene saponin was approved in marketed vaccines as an adjuvant due to the formation of immunostimulating complexes. Immunostimulating complexes consist of a Quillaja saponin, cholesterol, phospholipids, and a corresponding antigen. Recently, another saponin from was successfully tested in immunostimulating complexes, too. Based on the results of interaction studies, the formation of drug delivery systems such as immunostimulating complexes or similar self-assembled colloids is postulated for a variety of saponins. [Mh] Termos MeSH primário: ISCOMs/química Saponinas/farmacologia Tomatina/análogos & derivados [Mh] Termos MeSH secundário: Animais Células Cultivadas Hemólise Membranas Artificiais Camundongos Modelos Biológicos Quillaja/química Saponinas/química Tomatina/química Tomatina/isolamento & purificação Tomatina/farmacologia Triterpenos/química Triterpenos/farmacologia [Pt] Tipo de publicação: JOURNAL ARTICLE; REVIEW [Nm] Nome de substância: 0 (ISCOMs); 0 (Membranes, Artificial); 0 (Saponins); 0 (Triterpenes); 0 (alpha-tomatine); 31U6547O08 (Tomatine) [Em] Mês de entrada: 1704 [Cu] Atualização por classe: 170428 [Lr] Data última revisão: 170428 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 161021 [St] Status: MEDLINE

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[PMID]: 27213896 [Au] Autor: Ventrella E; Adamski Z; Chudzinska E; Miadowicz-Kobielska M; Marciniak P; Büyükgüzel E; Büyükgüzel K; Erdem M; Falabella P; Scrano L; Bufo SA [Ad] Endereço: Department of Sciences, University of Basilicata, Potenza, Italy. [Ti] Título: Solanum tuberosum and Lycopersicon esculentum Leaf Extracts and Single Metabolites Affect Development and Reproduction of Drosophila melanogaster. [So] Source: PLoS One;11(5):e0155958, 2016. [Is] ISSN: 1932-6203 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Glycoalkaloids are secondary metabolites commonly found in Solanaceae plants. They have anti-bacterial, anti-fungal and insecticidal activities. In the present study we examine the effects of potato and tomato leaf extracts and their main components, the glycoalkaloids α-solanine, α-chaconine and α-tomatine, on development and reproduction of Drosophila melanogaster wild-type flies at different stages. Parental generation was exposed to five different concentrations of tested substances. The effects were examined also on the next, non-exposed generation. In the first (exposed) generation, addition of each extract reduced the number of organisms reaching the pupal and imaginal stages. Parent insects exposed to extracts and metabolites individually applied showed faster development. However, the effect was weaker in case of single metabolites than in case of exposure to extracts. An increase of developmental rate was also observed in the next, non-exposed generation. The imagoes of both generations exposed to extracts and pure metabolites showed some anomalies in body size and malformations, such as deformed wings and abdomens, smaller black abdominal zone. Our results further support the current idea that Solanaceae can be an impressive source of molecules, which could efficaciously be used in crop protection, as natural extract or in formulation of single pure metabolites in sustainable agriculture. [Mh] Termos MeSH primário: Drosophila melanogaster/fisiologia Lycopersicon esculentum/química Extratos Vegetais/farmacologia Reprodução/efeitos dos fármacos Solanum tuberosum/química [Mh] Termos MeSH secundário: Animais Tamanho Corporal/efeitos dos fármacos Drosophila melanogaster/efeitos dos fármacos Drosophila melanogaster/crescimento & desenvolvimento Feminino Masculino Controle Biológico de Vetores Extratos Vegetais/química Folhas de Planta/química Solanina/análogos & derivados Solanina/farmacologia Tomatina/análogos & derivados Tomatina/farmacologia [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Plant Extracts); 0 (alpha-solanine); 0 (alpha-tomatine); 20562-02-1 (Solanine); 20562-03-2 (alpha-chaconine); 31U6547O08 (Tomatine) [Em] Mês de entrada: 1707 [Cu] Atualização por classe: 170713 [Lr] Data última revisão: 170713 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 160524 [St] Status: MEDLINE [do] DOI: 10.1371/journal.pone.0155958

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[PMID]: 27173549 [Au] Autor: Yamashoji S; Onoda E [Ad] Endereço: Department of Materials and Life Science, Shizuoka Institute of Science and Technology, 2200 Toyosawa, Fukuroi city, Shizuoka, Japan; Microbial Technology Laboratory, 9-50-514 Kaigan-dori, Tarumi-ku, Kobe city 655-0036, Hyogo, Japan. Electronic address: ss.yamashoji@hotmail.co.jp. [Ti] Título: Detoxification and function of immature tomato. [So] Source: Food Chem;209:171-6, 2016 Oct 15. [Is] ISSN: 0308-8146 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: α-Tomatine and chlorophyll (a and b) decreased, and ß-carotene and lycopene increased with ripening of tomatoes. α-Tomatine was localised in peel of immature green tomatoes. The dose-response curve of α-tomatine determined by WST-1 (water soluble tetrazolium) assay was the same as that by LDH (lactate dehydrogenase) assay, suggesting that the cytotoxicity of α-tomatine depends on the destruction of plasma membrane. Immature green tomatoes had little cytotoxic effect after one month-incubation with 25% ethanol or 4.5% acetate at 7°C, and α-tomatine was decomposed by crude enzymes extracted from immature green tomatoes. Immature green tomatoes incubated with 4.5% acetic acid inhibited the accumulation of lipid in adipocytes. From the above facts the detoxification and the anti-obesity effect of immature green tomatoes are expected to be controlled by the removal of peel, the enzymatic decomposition or the incubation with 4.5% acetate or 25% ethanol. [Mh] Termos MeSH primário: Frutas/química Lycopersicon esculentum/crescimento & desenvolvimento Tomatina/análogos & derivados [Mh] Termos MeSH secundário: Animais Carotenoides/análise Carotenoides/metabolismo Clorofila/análise Clorofila/metabolismo Frutas/crescimento & desenvolvimento Frutas/metabolismo Lycopersicon esculentum/química Lycopersicon esculentum/metabolismo Camundongos Células NIH 3T3 Ratos Tomatina/análise Tomatina/metabolismo beta Caroteno/análise beta Caroteno/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (alpha-tomatine); 01YAE03M7J (beta Carotene); 1406-65-1 (Chlorophyll); 31U6547O08 (Tomatine); 36-88-4 (Carotenoids); SB0N2N0WV6 (lycopene); YF5Q9EJC8Y (chlorophyll a) [Em] Mês de entrada: 1701 [Cu] Atualização por classe: 170123 [Lr] Data última revisão: 170123 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 160514 [St] Status: MEDLINE

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[PMID]: 26777454 [Au] Autor: Alonso PE; Rioja LF [Ad] Endereço: Department of Plastic Surgery, University Hospital Reina Sofía, Avda. Menéndez Pidal S/N, 14004 Córdoba, Spain. Electronic address: pedroalonso13@hotmail.com. [Ti] Título: Solanidine and tomatidine trigger scar pruritus. [So] Source: Burns;42(3):535-40, 2016 May. [Is] ISSN: 1879-1409 [Cp] País de publicação: Netherlands [La] Idioma: eng [Ab] Resumo: Scar pruritus is frequently encountered in clinical practice (particularly in burn patients) owing to its poorly known pathogenesis and difficult treatment. In previous work, we demonstrated the usefulness of a diet excluding edible solanaceae (viz., potatoes, tomatoes, peppers and aubergines) in patients with antihistamine-resistant scar pruritus. We hypothesized that alkaloids in solanaceae (particularly their secondary metabolites or aglycones) might be the actual pruritogens. In order to test this hypothesis, we conducted a single-blind prospective study on patients responding favourably to a solanaceae-free diet whose scar pruritus could be ascribed to one of the four foods. The study involved applying the aglycones solanidine and tomatidine to each scar and checking whether, and which, had a pruritogenic effect. A total of 18 patients (90%) responded by developing pruritus; also, the triggering aglycone coincided with that prevailing in the pruritogenic food. We concluded that solanaceae aglycones are directly involved in the pathogenesis of scar pruritus. [Mh] Termos MeSH primário: Diosgenina/efeitos adversos Prurido/induzido quimicamente Alcaloides de Solanáceas/efeitos adversos Tomatina/análogos & derivados [Mh] Termos MeSH secundário: Administração Cutânea Adulto Idoso Queimaduras/complicações Cicatriz Hipertrófica/etiologia Feminino Seres Humanos Queloide/etiologia Masculino Meia-Idade Estudos Prospectivos Prurido/dietoterapia Prurido/etiologia Método Simples-Cego Solanaceae Ferida Cirúrgica/complicações Tomatina/efeitos adversos Adulto Jovem [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Solanaceous Alkaloids); 2B73S48786 (tomatidine); 31U6547O08 (Tomatine); K49P2K8WLX (Diosgenin); W7801OHM8B (solanidine) [Em] Mês de entrada: 1703 [Cu] Atualização por classe: 170817 [Lr] Data última revisão: 170817 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 160119 [St] Status: MEDLINE

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[PMID]: 25820039 [Au] Autor: Jiang QW; Chen MW; Cheng KJ; Yu PZ; Wei X; Shi Z [Ad] Endereço: Department of Cell Biology & Institute of Biomedicine, National Engineering Research Center of Genetic Medicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou, 510632, Guangdong, China. [Ti] Título: Therapeutic Potential of Steroidal Alkaloids in Cancer and Other Diseases. [So] Source: Med Res Rev;36(1):119-43, 2016 Jan. [Is] ISSN: 1098-1128 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Steroidal alkaloids are a class of secondary metabolites isolated from plants, amphibians, and marine invertebrates. Evidence accumulated in the recent two decades demonstrates that steroidal alkaloids have a wide range of bioactivities including anticancer, antimicrobial, anti-inflammatory, antinociceptive, etc., suggesting their great potential for application. It is therefore necessary to comprehensively summarize the bioactivities, especially anticancer activities and mechanisms of steroidal alkaloids. Here we systematically highlight the anticancer profiles both in vitro and in vivo of steroidal alkaloids such as dendrogenin, solanidine, solasodine, tomatidine, cyclopamine, and their derivatives. Furthermore, other bioactivities of steroidal alkaloids are also discussed. The integrated molecular mechanisms in this review can increase our understanding on the utilization of steroidal alkaloids and contribute to the development of new drug candidates. Although the therapeutic potentials of steroidal alkaloids look promising in the preclinical and clinical studies, further pharmacokinetic and clinical studies are mandated to define their efficacy and safety in cancer and other diseases. [Mh] Termos MeSH primário: Alcaloides/uso terapêutico Neoplasias/tratamento farmacológico Esteroides/uso terapêutico [Mh] Termos MeSH secundário: Alcaloides/química Androgênios/química Animais Anti-Inflamatórios/química Antineoplásicos/química Linhagem Celular Tumoral Diosgenina/química Estrogênios/química Seres Humanos Camundongos Alcaloides de Solanáceas/química Tomatina/análogos & derivados Tomatina/química Alcaloides de Veratrum/química [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW [Nm] Nome de substância: 0 (Alkaloids); 0 (Androgens); 0 (Anti-Inflammatory Agents); 0 (Antineoplastic Agents); 0 (Estrogens); 0 (Solanaceous Alkaloids); 0 (Steroids); 0 (Veratrum Alkaloids); 2B73S48786 (tomatidine); 31U6547O08 (Tomatine); K49P2K8WLX (Diosgenin); L40Y453Y96 (solasodine); W7801OHM8B (solanidine); ZH658AJ192 (cyclopamine) [Em] Mês de entrada: 1609 [Cu] Atualização por classe: 151215 [Lr] Data última revisão: 151215 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 150331 [St] Status: MEDLINE [do] DOI: 10.1002/med.21346

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[PMID]: 26630272 [Au] Autor: Huang H; Chen X; Li D; He Y; Li Y; Du Z; Zhang K; DiPaola R; Goodin S; Zheng X [Ad] Endereço: Allan H. Conney Laboratory for Anticancer Research, Guangdong University of Technology, Guangzhou, P. R. China. [Ti] Título: Combination of α-Tomatine and Curcumin Inhibits Growth and Induces Apoptosis in Human Prostate Cancer Cells. [So] Source: PLoS One;10(12):e0144293, 2015. [Is] ISSN: 1932-6203 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: α-Tomatine is a glycoalkaloid found in tomatoes and curcumin is a major yellow pigment of turmeric. In the present study, the combined effect of these two compounds on prostate cancer cells was studied. Treatment of different prostate cancer cells with curcumin or α-tomatine alone resulted in growth inhibition and apoptosis in a concentration-dependent manner. Combinations of α-tomatine and curcumin synergistically inhibited the growth and induced apoptosis in prostate cancer PC-3 cells. Effects of the α-tomatine and curcumin combination were associated with synergistic inhibition of NF-κB activity and a potent decrease in the expression of its downstream gene Bcl-2 in the cells. Moreover, strong decreases in the levels of phospho-Akt and phosphor-ERK1/2 were found in PC-3 cells treated with α-tomatine and curcumin in combination. In animal experiment, SCID mice with PC-3 xenograft tumors were treated with α-tomatine and curcumin. Combination of α-tomatine and curcumin more potently inhibited the growth of PC-3 tumors than either agent alone. Results from the present study indicate that α-tomatine in combination with curcumin may be an effective strategy for inhibiting the growth of prostate cancer. [Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia Apoptose/efeitos dos fármacos Proliferação Celular/efeitos dos fármacos Curcumina/farmacologia Neoplasias da Próstata/tratamento farmacológico Tomatina/análogos & derivados [Mh] Termos MeSH secundário: Animais Antineoplásicos/farmacologia Linhagem Celular Tumoral Seres Humanos Sistema de Sinalização das MAP Quinases/efeitos dos fármacos Masculino Camundongos Camundongos SCID NF-kappa B/metabolismo Fosforilação/efeitos dos fármacos Próstata/efeitos dos fármacos Próstata/metabolismo Neoplasias da Próstata/metabolismo Proteínas Proto-Oncogênicas c-akt/metabolismo Proteínas Proto-Oncogênicas c-bcl-2/metabolismo Transdução de Sinais/efeitos dos fármacos Tomatina/farmacologia [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Antineoplastic Agents); 0 (NF-kappa B); 0 (Proto-Oncogene Proteins c-bcl-2); 0 (alpha-tomatine); 31U6547O08 (Tomatine); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); IT942ZTH98 (Curcumin) [Em] Mês de entrada: 1606 [Cu] Atualização por classe: 170220 [Lr] Data última revisão: 170220 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 151203 [St] Status: MEDLINE [do] DOI: 10.1371/journal.pone.0144293

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