RESUMO
In clinical, Psychotria serpens L. was often substitute for Caulis trachelospermi to treat cancer in China. Meanwhile, EtOAc and n-BuOH fractions of MeOH extract of P. serpens L. show power activity against H460, HepG2, Hela, and PC9/GR cell lines, and no toxic effects against normal 16HBE cell lines. In our ongoing search for bioactive novel compounds from Chinese material medica, one new type of glycosylsphingolipids Psychotramide (1a-1c) were isolated from P. serpens L., and their structures were identified through spectroscopic techniques including NMR (1D and 2D) and MS (LC-MS, and GC-MS).
Assuntos
Glicoesfingolipídeos/isolamento & purificação , Psychotria/química , Linhagem Celular , China , Cromatografia Gasosa-Espectrometria de Massas , Glicoesfingolipídeos/química , Glicoesfingolipídeos/farmacologia , Humanos , Medicina Tradicional Chinesa , Estrutura Molecular , Análise EspectralRESUMO
The stem bark of Euonymus japonicus Thunb. led to the isolation of three new glycosylsphingolipids (1-3), 1-O-[-L-rhamnopyranosyl-(1â2)-ß-D-glucopyranosyl]-(2S,3R,9E)-2-N-[(2R)-hydroxystearoyl]-octadecasphinga-9-ene (euojaposphingoside A, 1), 1-O-[ß-D-glucopyranosyl-(1â2)-ß-D-glucopyranosyl]-(2S,3R,4R,11E)-2-N-[(2R)-hydroxydocasanoyl]-octadecasphinga-11-ene (euojaposphingoside B, 2), 1-O-[ß-D-glucopyranosyl]-2'-O-[ß-D-glucopyranosyl]-(2S,3R,4R,11E)-2-N-[(2R)-hydroxytetracosanoyl]-octadecasphinga-11-ene (euojaposphingoside C, 3) along with three known glycosylsphingolipids (4-6), 1-O-[ß-D-glucopyranosyl]-(2S,3R,9E)-3-hydroxymethyl-2-N-[(2R)-hydroxynonacosanoyl)-tridecasphinga-9-ene (4), 1-O-[ß-D-glucopyranosyl]-(2S,3R,9E,12E)-2-N-[(2R)-hydroxytetracosanoyl] octadecasphinga-9,12-diene (5), 1-O-[ß-D-glucopyranosyl]-(2S,3R,5R,9E)-2-N-[tridecanoyl] nonacosasphinga-9-ene (6), lupeol (7), stigmasterol (8), sitosterol (ß and α) (9,10) and ß-carotene (11). The structure of all the compounds was achieved by spectroscopic and chemical data analysis. The antiplasmodial, antileismanial and cytotoxic activity of all compounds was tested.
Assuntos
Euonymus/química , Glicoesfingolipídeos/isolamento & purificação , Extratos Vegetais/química , Animais , Glicoesfingolipídeos/química , Glicoesfingolipídeos/farmacologia , Leishmania/efeitos dos fármacos , Estrutura Molecular , Mioblastos/efeitos dos fármacos , Casca de Planta/química , Extratos Vegetais/farmacologia , Caules de Planta/química , Plasmodium falciparum/efeitos dos fármacos , RatosRESUMO
Rhizochalin is a two-headed sphingolipid-like compound isolated from the sponge Rhizochalina incrustata. It has been reported that rhizocalin and its derivates have a chemopreventive and chemotherapeutic effect. However, the molecular mechanism of these effects is not understood. Here, we demonstrate that aglycon of rhizochalin (AglRhz) from the Rhizochalina incrustata induces AMP-activated protein kinase (AMPK) phosphorylation, and thereby inhibits mammalian target of rapamycin (mTOR)-p70S6 kinase-extracellular signal-regulated kinase (ERK) signaling and activator protein 1 (AP-1) activity via phosphorylation of Raptor in HT-29 cells. In addition, AglRhz induced activation of caspase-3 and poly(ADP-ribose) polymerase (PARP), and DNA fragmentation in HT-29 cells, leads to induction of apoptosis as well as suppression of tumorigenicity of HT-29 cells. Notably, AglRhz inhibits insulin-like growth factor (IGF)-1-induced AP-1 activity and cell transformation in JB6 Cl41 cells. Overall, our findings identify AMPK as an important target protein for mediating the anti-tumor properties of AglRhz in HT-29 colon cancer cells and have important implication for sponges, the most important marine source, in colon cancer.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Antineoplásicos/farmacologia , Quimioprevenção , Neoplasias do Colo/tratamento farmacológico , Álcoois Graxos/farmacologia , Glicoesfingolipídeos/farmacologia , Proteínas Quinases Ativadas por AMP/genética , Animais , Antineoplásicos/metabolismo , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Transformação Celular Neoplásica/efeitos dos fármacos , Neoplasias do Colo/enzimologia , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Fragmentação do DNA/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Álcoois Graxos/metabolismo , Álcoois Graxos/uso terapêutico , Glicoesfingolipídeos/química , Glicoesfingolipídeos/metabolismo , Glicoesfingolipídeos/uso terapêutico , Células HT29 , Humanos , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Terapia de Alvo Molecular , Oceanos e Mares , Fosforilação , Fitoterapia , Preparações de Plantas/química , Preparações de Plantas/isolamento & purificação , Preparações de Plantas/farmacologia , Poli(ADP-Ribose) Polimerases/metabolismo , Poríferos , Proteínas Serina-Treonina Quinases/metabolismo , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Sais de Tetrazólio , Tiazóis , Células Tumorais CultivadasRESUMO
We describe the use of a phage-displayed random pentadecamer peptide library for searching glycosphingolipid mimicking peptides. Two phage clones (AD-1 and AD-2) were selected by biopanning using monoclonal antibody AD117m, directed to lactotetraosylceramide (Lc4Cer). The amino acid sequences of the selected clones showed high homology (VPPXFXXXY) in 9-mer. Three phage clones were selected by using monoclonal antibody H11, directed to neolactotetraosylceramide (nLc4Cer), the linkage isomer of Lc4Cer, and the displayed amino acid sequences were compared. One of these peptides showed the same amino acid sequence as that of AD-2 except for one amino acid substitution. Pentadecamer, 9-mer and point mutated 9-mer peptides were synthesized on the basis of the displayed amino acid sequences. Binding activity of the peptides to the monoclonal antibodies or Ricinus communis lectin showed that 9-mer peptides are enough to mimic the epitope carbohydrate structure. Furthermore, six of the synthesized peptides inhibited Jack bean beta-galactosidase activity towards nLc4Cer at a high concentration of the enzyme, whereas at lower enzyme concentrations some peptides showed potent activation of the enzyme activity. This is the first report of carbohydrate mimicking peptides which modulate glycosidase activity.