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1.
Nutrients ; 10(6)2018 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-29799481

RESUMO

The aim of this study is to investigate the potential inhibitory effect of α-chaconine and α-solanine on RL95-2 estrogen receptor (ER) positive human endometrial cancer cell line and to identify the effect of these glycoalkaloids on the Akt signaling and ERα. The cell proliferation profiles and the cytotoxicity studies were performed by Real-Time Cell Analyzer (xCELLigence) and compared with Sulphorhodamine B (SRB) assay. The effects of α-chaconine (2.5, 5, 10 µM), α-solanine (20, 30, 50 µM), API-1 (25 µM) and MPP (20 µM) effects on Akt (Ser473) and ERα (Ser167) expressions evaluated by Western blot and qPCR method. Their IC50 values were as α-chaconine (4.72 µM) < MPP (20.01 µM) < α-solanine (26.27 µM) < API-1 (56.67 µM). 10 µM α-chaconine and 20, 30 and 50 µM α-solanine were effective in decreasing p-Akt(Ser473)/Akt ratio compared to positive control API-1. When the p-ERα/ERα ratios were evaluated, it was observed that α-chaconine (2.5, 5, 10 µM) and α-solanine (50 µM) were as effective as the specific ERα inhibitor MPP in reducing the ratio of p-ERα/ERα compared to the control group. In conclusion, it has been shown that the proliferation of α-chaconine and α-solanine in human endometrial carcinoma cells reduces the expression and activity of the Akt and ERα signaling pathway.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Neoplasias do Endométrio/tratamento farmacológico , Receptor alfa de Estrogênio/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Solanina/análogos & derivados , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Regulação para Baixo , Neoplasias do Endométrio/enzimologia , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Receptor alfa de Estrogênio/genética , Feminino , Humanos , Concentração Inibidora 50 , Fosforilação , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais/efeitos dos fármacos , Solanina/farmacologia , Fatores de Tempo
2.
Chem Biol Interact ; 235: 85-94, 2015 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-25913072

RESUMO

In this study, we investigated the molecular mechanisms underlying the anti-inflammatory effects of α-chaconine in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages and in LPS-induced septic mice. α-Chaconine inhibited the expressions of cyclooxygenase-2 (COX-2), interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-α (TNF-α) at the transcriptional level, and attenuated the transcriptional activity of activator protein-1 (AP-1) by reducing the translocation and phosphorylation of c-Jun. α-Chaconine also suppressed the phosphorylation of TGF-ß-activated kinase-1 (TAK1), which lies upstream of mitogen-activated protein kinase kinase 7 (MKK7)/Jun N-terminal kinase (JNK) signaling. JNK knockdown using siRNA prevented the α-chaconine-mediated inhibition of pro-inflammatory mediators. In a sepsis model, pretreatment with α-chaconine reduced the LPS-induced lethality and the mRNA and production levels of pro-inflammatory mediators by inhibiting c-Jun activation. These results suggest that the anti-inflammatory effects of α-chaconine are associated with the suppression of AP-1, and support its possible therapeutic role for the treatment of sepsis.


Assuntos
Endotoxinas/metabolismo , Inflamação/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Solanina/análogos & derivados , Solanum tuberosum/química , Fator de Transcrição AP-1/metabolismo , Animais , Linhagem Celular , Ciclo-Oxigenase 2/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , MAP Quinase Quinase 4/metabolismo , MAP Quinase Quinase 7 , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fosforilação/efeitos dos fármacos , Solanina/farmacologia , Fator de Crescimento Transformador beta/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
3.
J Agric Food Chem ; 63(13): 3323-37, 2015 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-25821990

RESUMO

Inhibition of cancer can occur via apoptosis, a genetically directed process of cell self-destruction that involves numerous biomarkers and signaling pathways. Glycoalkaloids are nitrogen-containing secondary plant metabolites found in numerous Solanaceous plants including eggplants, potatoes, and tomatoes. Exposure of cancer cells to glycoalkaloids produced by eggplants (α-solamargine and α-solasonine), potatoes (α-chaconine and α-solanine), and tomatoes (α-tomatine) or their hydrolysis products (mono-, di-, and trisaccharide derivatives and the aglycones solasodine, solanidine, and tomatidine) inhibits the growth of the cells in culture (in vitro) as well as tumor growth in vivo. This overview comprehensively surveys and consolidates worldwide efforts to define the following aspects of these natural compounds: (a) their prevalence in the three foods; (b) their chemistry and structure-activity relationships; (c) the reported factors (biomarkers, signaling pathways) associated with apoptosis of bone, breast, cervical, colon, gastric, glioblastoma, leukemia, liver, lung, lymphoma, melanoma, pancreas, prostate, and squamous cell carcinoma cell lines in vitro and the in vivo inhibition of tumor formation and growth in fish and mice and in human skin cancers; and (d) future research needs. The described results may make it possible to better relate the structures of the active compounds to their health-promoting function, individually, in combination, and in food, and allow the consumer to select glycoalkaloid-containing food with the optimal content of nontoxic beneficial compounds. The described findings are expected to be a valuable record and resource for further investigation of the health benefits of food-related natural compounds.


Assuntos
Anticarcinógenos , Alcaloides de Solanáceas/química , Alcaloides de Solanáceas/farmacologia , Solanum lycopersicum/metabolismo , Solanum melongena/metabolismo , Solanum tuberosum/metabolismo , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Camundongos , Alcaloides de Solanáceas/biossíntese , Solanina/análogos & derivados , Solanina/farmacologia , Relação Estrutura-Atividade , Tomatina/análogos & derivados , Tomatina/farmacologia
4.
Food Chem ; 141(2): 669-74, 2013 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-23790833

RESUMO

α-Solanine and α-chaconine are well-known potato toxins, but the mechanism of the synergistic cytotoxic effect of these alkaloids has been little clarified. This study confirmed their synergistic cytotoxic effects on C6 rat glioma cells by three different cell viability tests, namely WST-1 (water-soluble tetrazolium) assay sensitive to intracellular NADH concentration, menadione-catalysed chemiluminescent assay depending on both NAD(P)H concentration and NAD(P)H:quinone reductase activity, and LDH (lactate dehydrogenase) assay sensitive to the release of LDH from damaged cells. The maximum cytotoxic effect was observed at a ratio of 1:1 between α-solanine and α-chaconine at micromolar concentrations. The cytotoxic effects of these alkaloids were observed immediately after incubation and were constant after 30min, suggesting that rapid damage of plasma membrane causes the lethal disorder of metabolism.


Assuntos
Solanina/análogos & derivados , Solanum tuberosum/química , Toxinas Biológicas/toxicidade , Animais , Transporte Biológico/efeitos dos fármacos , Linhagem Celular Tumoral , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Sobrevivência Celular/efeitos dos fármacos , NAD/metabolismo , Ratos , Solanina/toxicidade
5.
Life Sci ; 92(13): 775-82, 2013 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-23454444

RESUMO

AIMS: The potato glycoalkaloids, α-chaconine, α-solanine and solanidine, along with potato peel extracts were investigated for potential anti-inflammatory effects in vitro. Their potential to reduce two biomarkers of inflammation, cytokine and nitric oxide (NO) productions, were assessed in the stimulated Jurkat and macrophage models, respectively. MAIN METHODS: Cytokine and nitric oxide productions were stimulated in Jurkat and Raw 264.7 macrophages with Concanavalin A (Con A; 25 µg/ml) and lipopolysaccaride (LPS; 1 µg/ml), respectively. Selective concentrations of glycoalkaloids and potato peel extracts were added simultaneously with Con A or LPS for 24h to investigate their potential to reduce inflammatory activity. KEY FINDINGS: α-Chaconine and solanidine significantly reduced interleukin-2 (IL-2) and interleukin-8 (IL-8) productions in Con A-induced Jurkat cells. The potato peel extracts did not influence cytokine production. In LPS-stimulated Raw macrophages, α-solanine, solanidine and two potato peel extracts significantly reduced induced NO production. SIGNIFICANCE: Our findings suggest that sub-cytotoxic concentrations of potato glycoalkaloids and potato peel extracts possess anti-inflammatory effects in vitro and with further investigation may be useful in the prevention of anti-inflammatory diseases.


Assuntos
Anti-Inflamatórios/farmacologia , Diosgenina/farmacologia , Células Jurkat/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Solanina/análogos & derivados , Animais , Linhagem Celular , Concanavalina A/imunologia , Humanos , Interleucina-2/imunologia , Interleucina-8/imunologia , Células Jurkat/imunologia , Lipopolissacarídeos/imunologia , Macrófagos/imunologia , Camundongos , Óxido Nítrico/imunologia , Solanina/farmacologia , Solanum tuberosum/química
6.
Food Chem ; 135(4): 2814-24, 2012 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-22980877

RESUMO

The polyphenol (phenolic acids, flavanols and flavonols) and glycoalkaloid (α-chaconine and α-solanine) contents of potato tubers grown in Luxembourg were analyzed by UPLC-DAD and HPLC-MS/MS separately in peel (approx. 2mm), outer (approx. 1cm) and inner flesh. Polyphenol contents decreased from the peel via the outer to the inner flesh and differed among the cultivars. The cultivars Vitelotte and Luminella had the highest polyphenol contents (5202 and 572 µg/g dry weight (DW) in the outer flesh), whereas Charlotte and Bintje had the lowest contents (19.5 and 48.0 µg/g DW). Chlorogenic acid and its isomers (neo- and cryptochlorogenic acid) were the major polyphenols. Glycoalkaloid contents were highest in the peel and lowest in the inner flesh, values in the flesh were below guideline limits in all cultivars. In conclusion, potatoes contribute to the daily intake of polyphenols and their consumption, thereby, may have positive effects on health.


Assuntos
Extratos Vegetais/análise , Polifenóis/análise , Solanina/análise , Solanum tuberosum/química , Cromatografia Líquida de Alta Pressão , Luxemburgo , Extratos Vegetais/metabolismo , Polifenóis/metabolismo , Solanina/análogos & derivados , Solanina/metabolismo , Solanum tuberosum/crescimento & desenvolvimento , Solanum tuberosum/metabolismo , Espectrometria de Massas em Tandem
7.
Nutr Cancer ; 62(5): 601-10, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20574921

RESUMO

We recently reported that colored potato extracts and an anthocyanin rich fraction suppressed lymph-node carcinoma of the prostate (LNCaP) and prostate cancer-3 (PC-3) prostate cancer cell proliferation and induced apoptosis via caspase-dependent and caspase-independent pathways. Chlorogenic acid, caffeic acid, gallic acid, catechin, malvidin, and glycoalkaloids (alpha-chaconine and solanine) have now been identified as the major bioactive components of potato, and their effects on LNCaP and PC-3 cell proliferation and apoptosis have been investigated. alpha-chaconine (5 microg/ml) and gallic acid (15 microg/ml) exhibited potent antiproliferative properties and increased cyclin-dependent kinase inhibitor p27 levels in both cell lines. Both alpha-chaconine and gallic acid induced poly [adenosine diphosphate (ADP)] ribose polymerase cleavage and caspase-dependent apoptosis in LNCaP cells; however, caspase-independent apoptosis through nuclear translocation of endonuclease G was observed in both LNCaP and PC-3 cells. alpha-chaconine and gallic acid activated c-Jun N-terminal protein kinase (JNK), and this response played a major role in induction of caspase-dependent apoptosis in LNCaP cells; whereas modulation of JNK and mitogen-activated protein kinase did not affect alpha-chaconine- and gallic acid-induced caspase-independent apoptosis. These results suggest that apoptosis induced by whole potato extracts in prostate cancer cell lines may be in part due to alpha-chaconine and gallic acid.


Assuntos
Apoptose/efeitos dos fármacos , Ácido Gálico/farmacologia , Extratos Vegetais/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Solanina/análogos & derivados , Solanum tuberosum/química , Antígenos CD1/análise , Caspases/fisiologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Inibidor de Quinase Dependente de Ciclina p27 , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/análise , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Masculino , Neoplasias da Próstata/patologia , Solanina/farmacologia
8.
Biol Pharm Bull ; 33(4): 622-30, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20410596

RESUMO

alpha-Chaconine, a naturally occurring steroidal glycoalkaloid in potato sprouts, was found to possess anti-carcinogenic properties, such as inhibiting proliferation, migration, invasion, and inducing apoptosis of tumor cells. However, the effect of alpha-chaconine on tumor angiogenesis remains unclear. In the present study, we examined the effect of alpha-chaconine on angiogenesis in vitro. Data demonstrated that alpha-chaconine inhibited proliferation of bovine aortic endothelial cells (BAECs) in a dose-dependent manner. When treated with non-toxic doses of alpha-chaconine, cell migration, invasion and tube formation were markedly suppressed. Furthermore, alpha-chaconine reduced the expression and activity of matrix metalloproteinase-2 (MMP-2), which is involved in angiogenesis. Our biochemical assays indicated that alpha-chaconine potently suppressed the phosphorylation of c-Jun N-terminal kinase (JNK), phosphatidylinositide-3 kinase (PI3K) and Akt, while it did not affect phosphorylation of extracellular signal regulating kinase (ERK) and p38. In addition, alpha-chaconine significantly increased the cytoplasmic level of inhibitors of kappaBalpha (IkappaBalpha) and decreased the nuclear level of nuclear factor kappa B (NF-kappaB), suggesting that alpha-chaconine could inhibit NF-kappaB activity. Furthermore, the treatment of inhibitors specific for JNK (SP600125), PI3K (LY294002) or NF-kappaB (pyrrolidine dithiocarbamate) to BAECs reduced tube formation. Taken together, the results suggested that alpha-chaconine inhibited migration, invasion and tube formation of BAECs by reducing MMP-2 activities, as well as JNK and PI3K/Akt signaling pathways and inhibition of NF-kappaB activity. These findings reveal a new therapeutic potential for alpha-chaconine on anti-angiogenic therapy.


Assuntos
Inibidores da Angiogênese/farmacologia , Metaloproteinase 2 da Matriz/metabolismo , Neovascularização Patológica/tratamento farmacológico , Extratos Vegetais/farmacologia , Solanina/análogos & derivados , Solanum tuberosum/química , Inibidores da Angiogênese/uso terapêutico , Animais , Bovinos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/fisiologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Plântula , Solanina/farmacologia , Solanina/uso terapêutico , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
9.
Dig Dis Sci ; 55(11): 3078-85, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20198430

RESUMO

BACKGROUND: Inflammatory bowel disease (IBD) may be initiated following disruption of the intestinal epithelial barrier. This disruption, in turn, permits luminal antigens unfettered access to the mucosal immune system and leads to an uncontrolled inflammatory response. Glycoalkaloids, which are found in potatoes, disrupt cholesterol-containing membranes such as those of the intestinal epithelium. Glycoalkaloid ingestion through potatoes may play a role in the initiation and/or perpetuation of IBD. AIM: To determine if commercial and high glycoalkaloids containing fried potato skins aggravate intestinal inflammation using two different animal models of IBD. METHODS: Fried potato skins from commercial potatoes containing low/medium glycoalkaloid levels and high glycoalkaloids potatoes were fed for 20 days to interleukin 10 gene-deficient mice and dextran sodium sulfate-induced colitic mice. Intestinal permeability, mucosal cytokine and myeloperoxidase levels and body weight were determined to assess intestinal injury. RESULTS: Deep frying potato skins markedly increased glycoalkaloid content. Interleukin 10 gene-deficient mice fed fried commercial potato skins with medium glycoalkaloid content exhibited significantly elevated levels of ileal IFN-γ relative to controls. Mice in the dextran sodium sulfate colitis model that were fed the same strain of potatoes demonstrated significantly elevated levels of pro-inflammatory cytokines IFN-γ, TNF-α, and IL-17 in the colon in addition to an enhanced colonic permeability. Inflammatory response was intensified when the mice were fed potatoes with higher glycoalkaloid contents. CONCLUSIONS: Our results demonstrate that consumption of potato skins containing glycoalkaloids can significantly aggravate intestinal inflammation in predisposed individuals.


Assuntos
Doença de Crohn/fisiopatologia , Doenças Inflamatórias Intestinais/fisiopatologia , Alcaloides de Solanáceas/efeitos adversos , Solanum tuberosum/química , Animais , Colite Ulcerativa , Culinária , Citocinas/análise , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Predisposição Genética para Doença , Doenças Inflamatórias Intestinais/induzido quimicamente , Doenças Inflamatórias Intestinais/genética , Mucosa Intestinal/metabolismo , Camundongos , Peroxidase/análise , Solanina/análogos & derivados , Solanina/análise
10.
J Agric Food Chem ; 56(18): 8745-52, 2008 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-18729378

RESUMO

We previously reported that exposure of the intestinal epithelial Caco-2 cell line to noncytotoxic concentrations of potato glycoalkaloids resulted in increased expression of cholesterol biosynthesis genes. Genes involved in mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/v-akt murine thymoma viral oncogene homologue (AKT) pathways and their downstream effectors such as Jun, c-Myc, and Fos also were induced. MAPK and PI3K/AKT pathways have been described to regulate the activity of sterol regulatory element binding transcription factors (SREBPs) and consequently the expression of cholesterol biosynthesis genes. In this study, to understand the mechanism of induction of cholesterol biosynthesis upon alpha-chaconine treatment, its effect on SREBP-2 protein levels was investigated. We also examined whether MAPK and PI3K/AKT pathways are required for the observed induction of these genes following exposure of cells to alpha-chaconine. Differentiated Caco-2 cells were pretreated with LY294002 (PI3K inhibitor), PD98059 (MEK1 inhibitor), or SP600125 (JNK inhibitor) or a combination of all inhibitors for 24 h prior to coincubation with 10 microM alpha-chaconine for 6 h. Significant increases in precursor and mature protein levels of SREBP-2 were observed after alpha-chaconine exposure. We also observed that alpha-chaconine treatment resulted in significant phosphorylation of AKT, extracellular signal related protein kinase (ERK), and c-jun N terminal protein kinase (JNK) but not that of p38. In general, the kinase inhibitor experiments revealed that phosphorylation of kinases of PI3K/AKT, ERK, and JNK pathways was not crucial for the induction of expression of cholesterol biosynthesis genes, with the exception of SC5DL. The transcription of this later gene was reduced when all three pathways were inhibited. On the basis of these results, it can be postulated that other mechanisms, which may be independent of the MAPK and PI3K/AKT pathways, including possibly post-translational activation of SREBP-2, may be more pivotal for the induction of cholesterol biosynthesis genes following exposure of intestinal cells to alpha-chaconine.


Assuntos
Colesterol/biossíntese , Colesterol/genética , Expressão Gênica/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Solanina/análogos & derivados , Solanum tuberosum/química , Células CACO-2 , Células Epiteliais/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Solanina/farmacologia , Proteína de Ligação a Elemento Regulador de Esterol 2/genética
11.
J Agric Food Chem ; 55(26): 11035-43, 2007 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-18044836

RESUMO

Alpha-chaconine, isolated from Solanum tuberosum Linn., is a naturally occurring steroidal glycoalkaloid in potato sprouts. Some reports demonstrated that alpha-chaconine had various anticarcinogenic properties. The aim of this study is to investigate the inhibitory effect of alpha-chaconine on lung adenocarcinoma cell metastasis in vitro. We chose the highly metastatic A549 cells, which were treated with various concentrations of alpha-chaconine to clarify the potential of inhibiting A549 cells invasion and migration. Data showed that alpha-chaconine inhibited A549 cell invasion/migration according to wound healing assay and Boyden chamber assay. Our results also showed that alpha-chaconine could inhibit phosphorylation of c-Jun N-terminal kinase (JNK) and Akt, whereas it did not affected phosphorylation of extracellular signal regulating kinase (ERK) and p38. In addition, alpha-chaconine significantly decreased the nuclear level of nuclear factor kappa B (NF-kappaB) and the binding ability of NF-kappaB. These results suggested that alpha-chaconine inhibited A549 cell metastasis by a reduction of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) activities involving suppression of phosphoinositide 3-kinase/Akt/NF-kappaB (PI3K/Akt/NF-kappaB) signaling pathway. Inhibiting metastasis by alpha-chaconine might offer a pivotal mechanism for its effective chemotherapeutic action.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , NF-kappa B/efeitos dos fármacos , Metástase Neoplásica/prevenção & controle , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Solanina/análogos & derivados , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , DNA/metabolismo , Humanos , Neoplasias Pulmonares , NF-kappa B/metabolismo , Invasividade Neoplásica/prevenção & controle , Fosforilação/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Solanina/farmacologia
12.
J Agric Food Chem ; 54(23): 8655-81, 2006 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-17090106

RESUMO

Potatoes, members of the Solanaceae plant family, serve as major, inexpensive low-fat food sources providing energy (starch), high-quality protein, fiber, and vitamins. Potatoes also produce biologically active secondary metabolites, which may have both adverse and beneficial effects in the diet. These include glycoalkaloids, calystegine alkaloids, protease inhibitors, lectins, phenolic compounds, and chlorophyll. Because glycoalkaloids are reported to be involved in host-plant resistance and to have a variety of adverse as well as beneficial effects in cells, animals, and humans, a need exists to develop a clearer understanding of their roles both in the plant and in the diet. To contribute to this effort, this integrated review presents data on the (a) history of glycoalkaloids; (b) glycoalkaloid content in different parts of the potato plant, in processed potato products, and in wild, transgenic, and organic potatoes; (c) biosynthesis, inheritance, plant molecular biology, and glycoalkaloid-plant phytopathogen relationships; (d) dietary significance with special focus on the chemistry, analysis, and nutritional quality of low-glycoalkaloid potato protein; (e) pharmacology and toxicology of the potato glycoalkaloids comprising alpha-chaconine and alpha-solanine and their hydrolysis products (metabolites); (f) anticarcinogenic and other beneficial effects; and (g) possible dietary consequences of concurrent consumption of glycoalkaloids and other biologically active compounds present in fresh and processed potatoes. An enhanced understanding of the multiple and overlapping aspects of glycoalkaloids in the plant and in the diet will benefit producers and consumers of potatoes.


Assuntos
Glicosídeos/metabolismo , Alcaloides de Solanáceas/metabolismo , Solanum tuberosum/metabolismo , Animais , Sequência de Carboidratos , Dieta , Glicosídeos/química , Glicosídeos/toxicidade , Humanos , Dados de Sequência Molecular , Fenômenos Fisiológicos Vegetais , Alcaloides de Solanáceas/química , Alcaloides de Solanáceas/farmacologia , Solanina/análogos & derivados , Solanina/química , Solanina/metabolismo , Solanina/farmacologia , Solanum tuberosum/química
13.
Food Chem Toxicol ; 44(6): 839-46, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16387404

RESUMO

Although alpha-chaconine, one of the two major potato trisaccharide glycoalkaloids, have shown cytotoxic effects on human cancer cells, the exact mechanism of this action of alpha-chaconine is not completely understood. In this study, we found that alpha-chaconine induced apoptosis of HT-29 cells in a time- and concentration-dependent manner by using flow cytometric analysis. We also found that caspase-3 activity and the active form of caspase-3 were increased 12 h after alpha-chaconine treatment. Caspase inhibitors, N-Ac-DEVD-CHO and Z-VAD-fmk, prevented alpha-chaconine-induced apoptosis, whereas alpha-chaconine-induced apoptosis was potentiated by PD98059, an extracellular signal-regulated kinase (ERK) inhibitor. However, pretreatment of the cells with LY294002 and SB203580, inhibitors of PI3K and p38, respectively, BAPTA-AM, an intracellular Ca(2+) chelator, and antioxidants such as N-acetylcysteine (NAC) and Trolox had no effect on the alpha-chaconine-induced cell death. In addition, phosphorylation of ERK was reduced by the treatment with alpha-chaconine. Moreover, alpha-chaconine-induced caspase-3 activity was further increased by the pretreatment with PD98059. Thus, the results indicate that alpha-chaconine induces apoptosis of HT-29 cells through inhibition of ERK and, in turn, activation of caspase-3.


Assuntos
Apoptose/efeitos dos fármacos , Caspases/metabolismo , Inibidores Enzimáticos/farmacologia , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Solanina/análogos & derivados , Caspase 3 , Ativação Enzimática/efeitos dos fármacos , Células HT29 , Humanos , Proteína Quinase 1 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 3 Ativada por Mitógeno/antagonistas & inibidores , Fosforilação/efeitos dos fármacos , Solanina/farmacologia
14.
J Agric Food Chem ; 53(15): 6162-9, 2005 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-16029012

RESUMO

Methods were devised for the isolation of large amounts of pure alpha-chaconine and alpha-solanine from Dejima potatoes and for the extraction and analysis of total glycoalkaloids from five fresh potato varieties (Dejima, Jowon, Sumi, Toya, and Vora Valley). These compounds were then evaluated in experiments using a tetrazolium microculture (MTT) assay to assess the anticarcinogenic effects of (a) the isolated pure glycoalkaloids separately, (b) artificial mixtures of the two glycoalkaloids, and (c) the total glycoalkaloids isolated from each of the five potato varieties. All samples tested reduced the numbers of the following human cell lines: cervical (HeLa), liver (HepG2), lymphoma (U937), stomach (AGS and KATO III) cancer cells and normal liver (Chang) cells. The results show that (a) the effects of the glycoalkaloids were concentration dependent in the range of 0.1-10 mug/mL (0.117-11.7 nmol/mL); (b) alpha-chaconine was more active than was alpha-solanine; (c) some mixtures exhibited synergistic effects, whereas other produced additive ones; (d) the different cancer cells varied in their susceptibilities to destruction; and (e) the destruction of normal liver cells was generally lower than that of cancer liver cells. The decreases in cell populations were also observed visually by reversed-phase microscopy. The results complement related observations on the anticarcinogenic potential of food ingredients.


Assuntos
Anticarcinógenos/administração & dosagem , Neoplasias/patologia , Solanina/análogos & derivados , Solanina/administração & dosagem , Solanum tuberosum/química , Antineoplásicos/administração & dosagem , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Dieta , Sinergismo Farmacológico , Feminino , Humanos , Neoplasias Hepáticas/patologia , Linfoma/patologia , Neoplasias/tratamento farmacológico , Tubérculos/química , Neoplasias Gástricas/patologia , Neoplasias do Colo do Útero/patologia
15.
J Agric Food Chem ; 52(10): 2832-9, 2004 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-15137822

RESUMO

As part of an effort to improve plant-derived foods such as potatoes, eggplants, and tomatoes, the antiproliferative activities against human colon (HT29) and liver (HepG2) cancer cells of a series of structurally related individual compounds were examined using a microculture tetrazolium (MTT) assay. The objective was to assess the roles of the carbohydrate side chain and aglycon part of Solanum glycosides in influencing inhibitory activities of these compounds. Evaluations were carried out with four concentrations each (0.1, 1, 10, and 100 microg/mL) of the the potato trisaccharide glycoalkaloids alpha-chaconine and alpha-solanine; the disaccharides beta(1)-chaconine, beta(2)-chaconine, and beta(2)-solanine; the monosaccharide gamma-chaconine and their common aglycon solanidine; the tetrasaccharide potato glycoalkaloid dehydrocommersonine; the potato aglycon demissidine; the tetrasaccharide tomato glycoalkaloid alpha-tomatine, the trisaccharide beta(1)-tomatine, the disaccharide gamma-tomatine, the monosaccharide delta-tomatine, and their common aglycon tomatidine; the eggplant glycoalkaloids solamargine and solasonine and their common aglycon solasodine; and the nonsteroidal alkaloid jervine. All compounds were active in the assay, with the glycoalkaloids being the most active and the hydrolysis products less so. The effectiveness against the liver cells was greater than against the colon cells. Potencies of alpha-tomatine and alpha-chaconine at a concentration of 1 microg/mL against the liver carcinoma cells were higher than those observed with the anticancer drugs doxorubicin and camptothecin. Because alpha-chaconine, alpha-solanine, and alpha-tomatine also inhibited normal human liver HeLa (Chang) cells, safety considerations should guide the use of these compounds as preventative or therapeutic treatments against carcinomas.


Assuntos
Alcaloides/farmacologia , Divisão Celular/efeitos dos fármacos , Neoplasias do Colo/patologia , Neoplasias Hepáticas/patologia , Solanina/análogos & derivados , Solanum/química , Alcaloides/química , Humanos , Hidrólise , Solanum lycopersicum/química , Solanina/farmacologia , Relação Estrutura-Atividade , Tomatina/farmacologia , Células Tumorais Cultivadas
16.
Trends Biotechnol ; 22(3): 147-51, 2004 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15036866

RESUMO

As one of the major agricultural crops, the cultivated potato is consumed each day by millions of people from diverse cultural backgrounds. A product of global importance, the potato tuber contains toxic glycoalkaloids (GAs) that cause sporadic outbreaks of poisoning in humans, as well as many livestock deaths. This article will discuss some aspects of the potato GAs, including their toxic effects and risk factors, methods of detection of GAs and biotechnological aspects of potato breeding. An attempt has been made to answer a question of vital importance - are potato GAs dangerous to humans and animals and, if so, to what extent?


Assuntos
Alcaloides de Solanáceas/farmacologia , Solanina/análogos & derivados , Solanum tuberosum/química , Anormalidades Induzidas por Medicamentos/etiologia , Animais , Divisão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Fenômenos Fisiológicos Celulares/efeitos dos fármacos , Dano ao DNA , Humanos , Intoxicação por Plantas/etiologia , Solanina/farmacologia , Vírus/efeitos dos fármacos
17.
J Agric Food Chem ; 51(1): 288-94, 2003 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-12502423

RESUMO

In our recent studies we have evidenced that repression of ADP-ribosylation factor (ARF) in potato plants results in 14-3-3 gene activation. The significant alteration in plant phenotype and in carbohydrate content clearly indicates that there may also be changes in other metabolite syntheses. In this paper we present the data on contents of compounds, occurring in transgenic potato tubers from field trial, known to be important for the human diet. We also determine which of the ARF-antisense plant features resulted from ARF repression. This determination was accomplished by the analysis of ARF-antisense plants transformed with cDNA encoding 14-3-3 protein in reverse orientation. The sucrose accumulation and the decrease in glycoalkaloids level were found to be characteristic features of all transgenic plants. The increase in antioxidant capacity of transgenic potato tubers should also be pointed out. The analysis of fat from modified potato tubers revealed a nutritionally valuable composition of fatty acids, including the significant increase of linoleic acid level.


Assuntos
Fatores de Ribosilação do ADP/fisiologia , Antioxidantes/metabolismo , Raízes de Plantas/metabolismo , Plantas Geneticamente Modificadas , Solanina/análogos & derivados , Solanum/genética , Solanum/metabolismo , Proteínas 14-3-3 , Fatores de Ribosilação do ADP/genética , Aminoácidos/análise , Antioxidantes/análise , Carboidratos/análise , DNA Antissenso/genética , Ácidos Graxos/análise , Flavonoides/análise , Expressão Gênica , Lipídeos/análise , Fenótipo , Proteínas de Plantas/análise , Raízes de Plantas/química , Solanina/análise , Solanum/química , Transformação Genética , Tirosina 3-Mono-Oxigenase/genética , Tirosina 3-Mono-Oxigenase/fisiologia
18.
Zhonghua Fu Chan Ke Za Zhi ; 28(2): 73-5, 121-2, 1993 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-8344084

RESUMO

Potato glycoalkaloids were extracted from potato sprout and then analyzed to determine their purity by using TLC and HPLC methods and compare with pure alpha-Solanine and alpha-Chaconine of Sigma. The result indicated that the purity of potato glycoalkaloids is 78. 31%, which contains 73.64% alpha-Solanine and 4.67% alpha-Chaconine. The LD50 of mice was 44.721 +/- 5.860 4 mg/kg. In order to determine the toxicity and teratogenicity of potato glycoalkaloids, the effect of potato glycoalkaloids on Kunming pregnant mice were studied. The results showed that: (1) potato glycoalkaloids have teratogenic effects on embryos of mice. It could induce neural tube defects (NTDs), and may be an important teratogen of NTDs. (2) potato glycoalkaloids have embryo toxicity. It could cause the death of embryos and result in absorbed and dead fetuses. (3) potato glycoalkaloids could evidently affect the development of embryos and lead to intrauterine growth retardation (IUGR). An interesting phenomena which just like the clinical manifestation of miscarriage in human being was noticed. If potato glycoalkaloids were given to the pregnant mice on the 5th or 6th day of gestation intraabdominally, vaginal bleeding and abortion would occur, and this has not been reported yet. The animal model of NTDs in this experiments supported our hypothesis that sprouted potato could be a teratogen of NTDs.


Assuntos
Anormalidades Induzidas por Medicamentos/etiologia , Defeitos do Tubo Neural/induzido quimicamente , Solanina/análogos & derivados , Solanina/toxicidade , Solanum tuberosum/química , Animais , Feminino , Morte Fetal/induzido quimicamente , Retardo do Crescimento Fetal/induzido quimicamente , Dose Letal Mediana , Camundongos , Gravidez , Solanina/isolamento & purificação
19.
Teratology ; 30(3): 371-81, 1984 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-6515563

RESUMO

Keeler et al. (78) showed that potato sprouts could be teratogens for the central nervous system in the Syrian hamster. We demonstrate here the same teratogenic effect from a British cultivar, Arran Pilot. Most of the activity was traced to the two solanidine triglycosides, alpha-chaconine and, at a higher dose level, alpha-solanine. Some possible implications for the study of human neural-tube defects are considered.


Assuntos
Anormalidades Induzidas por Medicamentos/etiologia , Defeitos do Tubo Neural/induzido quimicamente , Solanina/análogos & derivados , Solanina/toxicidade , Verduras , Animais , Cricetinae , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Mesocricetus , Gravidez , Fatores Sexuais , Verduras/análise
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