RESUMO
Bee venom (BV), secreted from the venom gland of the honey bee, contains several biological active compounds. BV has been widely used as a traditional medicine for treating human disease, including cancer. In this study, we have shown the molecular mechanism underlying the therapeutic effect of BV on cancer. Treatment with BV reduced the proliferation of cervical-cancer cells in a dose- and time-dependent manner. Interestingly, the killing effect of BV was specific to HPVpositive cervical-cancer cell lines, such as Caski and HeLa cells, and not to HPV-negative cervical-cancer cells (C33A). BV reduced the expression of HPV E6 and E7 at RNA and protein levels, leading to an increase in the expression of p53 and Rb in Caski and HeLa cells. Further, BV decreased the levels of cell-cycle proteins, such as cyclin A and B, and increased the levels of cell-cycle inhibitors, such as p21 and p27. BV significantly induced apoptosis and inhibited wound healing and migration of cervical-cancer cells. It also upregulated the expression of pro-apoptotic BAX and downregulated the expression of anti-apoptotic Bcl-2 and Bcl-XL. Cleavage of caspase-3, caspase-9, and PARP were also induced by BV treatment, whereas the phosphorylation of mitogenic signalingrelated proteins, such as AKT, JNK, p38, and ERK, were downregulated. Our results indicate that BV has a therapeutic selectivity for HPV-positive malignant cells, so further clinical studies are needed to assess its clinical application. [BMB Reports 2020; 53(8): 419-424].
Assuntos
Venenos de Abelha/farmacologia , Neoplasias do Colo do Útero/tratamento farmacológico , Apoptose/efeitos dos fármacos , Venenos de Abelha/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Feminino , Células HeLa , Humanos , Proteínas Oncogênicas Virais/genética , Proteínas Oncogênicas Virais/metabolismo , Proteínas E7 de Papillomavirus/genética , Proteínas E7 de Papillomavirus/metabolismo , Infecções por Papillomavirus/tratamento farmacológico , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Transdução de Sinais/efeitos dos fármacos , Neoplasias do Colo do Útero/metabolismoRESUMO
Activation of peroxisome proliferator-activated receptors (PPARs) plays a crucial role in cellular energy metabolism that directly impacts mitochondrial biogenesis. In this study, we demonstrate that syringaresinol, a pharmacological lignan extracted from Panax ginseng berry, moderately binds to and activates PPARß with KD and EC50 values of 27.62±15.76µM and 18.11±4.77µM, respectively. Subsequently, the expression of peroxisome proliferator-activated receptor γ coactivator-1α together with PPARß transcriptional targets, mitochondrial carnitine palmitoyltransferase 1 and uncoupling protein 2, was also enhanced in terms of both mRNA and protein levels. The activation of these proteins induced mitochondrial biogenesis by enrichment of mitochondrial replication and density within C2C12 myotubes. Importantly, knockdown of PPARß reduced the syringaresinol-induced protein expression followed by the significant reduction of mitochondrial biogenesis. Taken together, our results indicate that syringaresinol induces mitochondrial biogenesis by activating PPARß pathway.
Assuntos
Furanos/química , Lignanas/química , Mitocôndrias/efeitos dos fármacos , PPAR beta/metabolismo , Animais , Carnitina O-Palmitoiltransferase/genética , Carnitina O-Palmitoiltransferase/metabolismo , Linhagem Celular , Furanos/isolamento & purificação , Furanos/farmacologia , Expressão Gênica/efeitos dos fármacos , Lignanas/isolamento & purificação , Lignanas/farmacologia , Camundongos , Mitocôndrias/metabolismo , Mioblastos/citologia , Mioblastos/metabolismo , PPAR beta/antagonistas & inibidores , PPAR beta/genética , Panax/química , Panax/metabolismo , Interferência de RNA , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/metabolismo , Proteína Desacopladora 2/genética , Proteína Desacopladora 2/metabolismoRESUMO
Syringaresinol exists either exclusively as one enantiomer or enantiomeric mixtures in plant foods. We found that (+)-syringaresinol, but not (-)-syringaresinol, upregulates silent information regulator two ortholog 1 (SIRT1) gene expression, and thus, Panax ginseng berry with predominantly high contents of (+)-syringaresinol exhibits higher activity in inducing SIRT1 gene expression than Acanthopanax senticosus Harms stem with almost equal proportion of the two enantiomers. These findings highlight the importance of the absolute configuration of syringaresinol for the biological activity.
Assuntos
Eleutherococcus/química , Frutas/química , Furanos/farmacologia , Lignanas/farmacologia , Panax/química , Extratos Vegetais/farmacologia , Sirtuína 1/genética , Proteína Forkhead Box O3 , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Regiões Promotoras Genéticas/genética , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sirtuína 1/metabolismo , Estereoisomerismo , Ressonância de Plasmônio de SuperfícieRESUMO
The complete nucleotide sequence of the chloroplast genome of potato Solanum tuberosum L. cv. Desiree was determined. The circular double-stranded DNA, which consists of 155,312 bp, contains a pair of inverted repeat regions (IRa, IRb) of 25,595 bp each. The inverted repeat regions are separated by small and large single copy regions of 18,373 and 85,749 bp, respectively. The genome contains 79 proteins, 30 tRNAs, 4 rRNAs, and unidentified genes. A comparison of chloroplast genomes of seven Solanaceae species revealed that the gene content and their relative positions of S. tuberosum are similar to the other six Solanaceae species. However, undefined open reading frames (ORFs) in LSC region were highly diverged in Solanaceae species except N. sylvestris. Detailed comparison was identified by numerous indels in the intergenic regions that were mostly located in the LSC region. Among them, a single large 241-bp deletion, was not associated with direct repeats and found in only S. tuberosum, clearly discriminates a cultivated potato from wild potato species Solanum bulbocastanum. The extent of sequence divergence may provide the basis for evaluating genetic diversity within the Solanaceae species, and will be useful to examine the evolutionary processes in potato landraces.
Assuntos
Agricultura , Pareamento de Bases , DNA de Cloroplastos/genética , Genoma de Planta/genética , Deleção de Sequência , Solanum tuberosum/genética , Sequência de Bases , DNA Intergênico/genética , Genes de Plantas , Íntrons/genética , Dados de Sequência Molecular , Mutação/genética , Fases de Leitura Aberta/genética , Filogenia , Sequências Repetitivas de Ácido Nucleico/genética , Alinhamento de Sequência , Homologia de Sequência do Ácido NucleicoRESUMO
Soy products are mainly composed of proteins, phytochemicals such as isoflavones, soy lipids, and carbohydrates. It is unclear whether an individual component alone or a combined effect of multiple bioactive compounds contributes to the beneficial properties of soy. We investigated the effect of dietary genistein (the principal soy isoflavone) alone and combined with L-carnitine to evaluate possible synergistic effects on the intentionally induced prediabetic state characterized by insulin resistance and obesity in C57Bl/6J mice fed a high-fat diet (HD). In the HD-alone group, abdominal and back fat relative to total body weight were significantly higher compared with other groups including those fed normal diet (ND). Among the HD groups, final weight gains of the HD plus genistein (HD+G) and HD plus genistein plus L-carnitine (HD+G+C) groups were lower compared with that of the control (HD-alone). Especially in liver, the results showed that genistein with carnitine transcriptionally up-regulated expressions of acyl-coenzyme A synthetase (ACS) and carnitine palmitoyltransferase-I (CPT-I) by approximately 50% and 40%, respectively, compared with genistein alone. However, the up-regulation of CPT-I did not directly reflect the enzyme activity of CPT-I. On the other hand, the effects of genistein and genistein with carnitine on the expressions of ACS and CPT-I in muscle were not significant. Our study suggests that genistein with carnitine exerts anti-obesity effects, probably by modulating peroxisome proliferator-activated receptor-associated genes. However, further work is needed to elucidate the possible mechanisms by which genistein and carnitine intervene.
Assuntos
Carnitina/administração & dosagem , Gorduras na Dieta/administração & dosagem , Genisteína/administração & dosagem , Lipídeos/sangue , Obesidade/prevenção & controle , Tecido Adiposo/anatomia & histologia , Tecido Adiposo/enzimologia , Animais , Carnitina/sangue , Carnitina O-Palmitoiltransferase/genética , Carnitina O-Palmitoiltransferase/metabolismo , Coenzima A Ligases/genética , Dieta , Sinergismo Farmacológico , Ácido Graxo Sintases/metabolismo , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Gliceraldeído-3-Fosfato Desidrogenases/genética , Gliceraldeído-3-Fosfato Desidrogenases/metabolismo , Resistência à Insulina , Leptina/sangue , Fígado/enzimologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Músculo Esquelético/enzimologia , Obesidade/enzimologia , RNA Mensageiro/análise , Distribuição Aleatória , Aumento de PesoRESUMO
Methyl jasmonate (MeJA) treatment increases the levels of plant secondary metabolites, including ginsenosides, which are considered to be the main active compounds in ginseng (Panax ginseng C.A. Meyer). To create a ginseng gene resource that contains the genes involved in the biosynthesis of secondary metabolites, including ginsenosides, we generated 3,134 expression sequence tags (ESTs) from MeJA-treated ginseng hairy roots. These ESTs assembled into 370 clusters and 1,680 singletons. Genes yielding highly abundant transcripts were those encoding proteins involved in fatty acid desaturation, the defense response, and the biosynthesis of secondary metabolites. Analysis of the latter group revealed a number of genes that may be involved in the biosynthesis of ginsenosides, namely, oxidosqualene cyclase (OSC), cytochrome P450, and glycosyltransferase. A novel OSC gene was also identified by this analysis. RNA gel blot analysis confirmed that transcription of this OSC gene, along with squalene synthase (SS) and squalene epoxidase (SE) gene transcription, is increased by MeJA treatment. This ginseng EST data set will also provide important information on the genes that are involved in the biosynthesis of other secondary metabolites and the genes that are responsive to MeJA treatment.