Questo lavoro è stato sostenuto dai Cavalieri di Colombo capitolo 9671 (Windsor, Ontario), e un CIHR Frederick Banting e Best Charles Canada Graduate Scholarship assegnato a Ma Dennis. Grazie a Hodge Robert ed Elizabeth Fidalgo da Silva per la loro assistenza con la microscopia time-lapse. Grazie a voi Katie Facecchia per la modifica dei time-lapse video microscopia. Vorremmo anche ringraziare Sudipa giugno Chatterjee e Phillip Tremblay per la revisione critica di questo manoscritto. Questo lavoro è dedicato in memoria di Kevin Couvillon che ha perso la sua battaglia contro il cancro nel 2010.

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Composti PST e simili hanno dimostrato di avere proprietà anti-cancro 11-15,21. Abbiamo precedentemente riportato PST naturale di destabilizzare selettivamente i mitocondri nelle cellule tumorali, che in tal modo induce apoptosi mediante il rilascio di fattori citotossici 12,14. E &#39;molto probabile che JCTH-4 agisce attraverso lo stesso meccanismo; JCTH-4 ha causato il collasso MMP in MCF7 come si è visto con colorazione TMRM (Fig. 5a), e una maggiore generazione di ROS nei mi...

<table border="1"><tbody><tr><td> Nome del materiale </td><td> Azienda </td><td> Numero di catalogo </td></tr><tr><td> SH-SY5Y linea cellulare </td><td> ATCC </td><td> CRL-2266 </td></tr><tr><td> Dulbecco Modified Eagles Medio F-12 HAM </td><td> Sigma-Aldrich </td><td> 51448C </td></tr><tr><td> Siero fetale bovino </td><td> Gibco BRL </td><td> 16000-044 </td></tr><tr><td> MCF7 linea cellulare </td><td> ATCC </td><td> HTB-22 </td></tr><tr><td> Mezzo RPMI-1640 </td><td> Sigma-Aldrich </td><td> R 0883 </td></tr><tr><td> A quanto pare umano normale linea cellulare di fibroblasti fetali (NFF) </td><td> Coriell Institute for Medical Research </td><td> AG04431B </td></tr><tr><td> Media Dulbeccòs Modified Eagle, medio alto glucosio </td><td> Thermo Scientific </td><td> SH30022.01 </td></tr><tr><td> Tamoxifene sale </td><td> Sigma-Aldrich </td><td> T9262 </td&gt; </tr><tr><td> 35 mm vetro di fondo della cultura piatti </td><td> MatTek </td><td> P35G-014-C </td></tr><tr><td> Leica DMI6000 B microscopio invertito </td><td> Leica Microsystems </td><td> N / A </td></tr><tr><td> Colorante Hoechst 33342 </td><td> Molecular Probes </td><td> H3570 </td></tr><tr><td> Leica DM IRB invertito microscopio a fluorescenza </td><td> Leica Microsystems </td><td> N / A </td></tr><tr><td> Annessina V AlexaFluor-488 </td><td> Invitrogen </td><td> A13201 </td></tr><tr><td> Trypan Blu soluzione </td><td> Sigma-Aldrich </td><td> T8154-20ML </td></tr><tr><td> Emocitometro </td><td> Fisher Scientific </td><td> 267110 </td></tr><tr><td> WST-1 reagente </td><td> Roche Applied Science </td><td> 11644807001 </td></tr><tr><td> Wallac Victor 3 1420 Multilabel contatore </td><td> PerkinElmer </td><td> 1420-011 </td></tr><tr><td> Tetrametilrodamina metilestere (TMRM) </td><td> Gibco BRL </td><td> T-668 </td></tr><tr><td> Glass tessuto grinder </td><td> Fisher Scientific </td><td> K8885300-0002 </td></tr><tr><td> BioRad proteine ​​test </td><td> Bio-Rad Laboratories </td><td> 500 0001Bottom della Forma </td></tr><tr><td> Amplex Red </td><td> Invitrogen </td><td> A12222 </td></tr><tr><td> Perossidasi di rafano (HRP) </td><td> Sigma-Aldrich </td><td> P8125 </td></tr><tr><td> Spectramax Gemini XPS </td><td> Molecular Devices </td><td> 3126666 </td></tr><tr><td> Anti-LC3 anticorpo cresciuto in coniglio </td><td> Novus Biologicals </td><td> NB100-2220 </td></tr><tr><td> Anti-mouse HRP-coniugato anticorpo secondario </td><td> Abcam </td><td> ab6728 </td></tr><tr><td> Anti-coniglio HRP-anticorpo secondario coniugato </td><td> Abcam </td><td> ab6802 </td></tr><tr><td> Chemiluminescenza perossidasi substrato </td><td> Sigma-Aldrich </td><td> CPS160 </td></tr><tr><td> Monodansylcadaverine </td><td> Sigma-Aldrich </td><td> 30432 </td></tr></tbody></table>

enhancement of apoptotic and autophagic induction by a novel synthetic c-1 analogue of 7-deoxypancratistatin in human breast adenocarcinoma and neuroblastoma cells with tamoxifen

Il cancro al seno è uno dei tumori più diffusi tra le donne in Nord America. Molti attuali trattamenti anti-tumorali, incluse le radiazioni ionizzanti, inducono apoptosi attraverso danni al DNA. Sfortunatamente, tali trattamenti non sono selettivi per le cellule tumorali e produrre tossicità simile in cellule normali. Abbiamo riportato l&#39;induzione di apoptosi selettiva in cellule tumorali dal pancratistatin composto naturale (PST). Recentemente, un romanzo PST analogico, un derivato C-1 di 7-acetossimetil deoxypancratistatin (JCTH-4), è stato prodotto mediante sintesi de novo e presenta comparabili selettiva attività inducente l&#39;apoptosi nelle linee cellulari tumorali diverse. Recentemente, autofagia è stato implicato in neoplasie sia come pro-sopravvivenza e pro-morte meccanismi in risposta alla chemioterapia. Tamoxifene (TAM) ha sempre dimostrato l&#39;induzione di pro-sopravvivenza autofagia in numerosi tumori. In questo studio, l&#39;efficacia di JCTH-4 da solo e in combinazione con TAM per indurre la morte cellulare in significatività maternor (MCF7) e neuroblastoma (SH-SY5Y) le cellule è stata valutata. TAM solo indotto l&#39;autofagia, ma la morte delle cellule insignificante, mentre JCTH-4 da sola ha causato significativa induzione di apoptosi con alcuni induzione di autofagia. È interessante notare che il trattamento combinatoria ha prodotto un drastico aumento di induzione di apoptosi e autofagia. Abbiamo monitorato le variazioni morfologiche tempo-dipendenti MCF7 cellule in fase di TAM-indotta autofagia, JCTH-4-indotta l&#39;apoptosi e l&#39;autofagia e morte cellulare accelerata con trattamento combinatoria utilizzando microscopia time-lapse. Abbiamo dimostrato questi composti di indurre apoptosi / autofagia per spese mitocondriale in queste cellule tumorali. È importante sottolineare che questi trattamenti non ha influenzato la sopravvivenza di fibroblasti umani non tumorali. Così, questi risultati indicano che JCTH-4 in combinazione con TAM potrebbe essere usato come un sicuro e molto potente terapia antitumorale contro il cancro al seno e cellule di neuroblastoma.

Watch this Scientific Journal Video about Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma 

Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen

Abbiamo sintetizzato un analogo romanzo di pancratistatin paragonabile attività anti-cancro come pancratistatin nativo; interessante, il trattamento con tamoxifene combinatoria ha prodotto un miglioramento drastico induzione apoptotica e autophagic da mitocondriale di mira con effetti minimi sui fibroblasti non tumorali. Così, JCTH-4 in combinazione con tamoxifene potrebbe fornire una sicura terapia antitumorale.

Valorizzazione dei induzione apoptotica e autofagica da un romanzo sintetico C-1 analogico di 7-deoxypancratistatin in adenocarcinoma del seno umano e cellule di neuroblastoma con Tamoxifene

Breast cancer is one of the most common cancers amongst women in North America. Many current anti-cancer treatments, including ionizing radiation, induce ...

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18.6K Views.  University of Windsor. Abbiamo sintetizzato un analogo romanzo di pancratistatin paragonabile attività anti-cancro come pancratistatin nativo; interessante, il trattamento con tamoxifene combinatoria ha prodotto un miglioramento drastico induzione apoptotica e autophagic da mitocondriale di mira con effetti minimi sui fibroblasti non tumorali. Così, JCTH-4 in combinazione con tamoxifene potrebbe fornire una sicura terapia antitumorale.

Video: Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen