A New Goniothalamin N-acylated Aza-derivative Strongly Downregulates Mediators Of Signaling Transduction Associated With Pancreatic Cancer Aggressiveness.

dc.creatorBarcelos, Rosimeire Coura
dc.creatorPelizzaro-Rocha, Karin Juliane
dc.creatorPastre, Julio Cezar
dc.creatorDias, Marina Pereira
dc.creatorFerreira-Halder, Carmen Veríssima
dc.creatorPilli, Ronaldo Aloise
dc.date2014-Nov
dc.date2015-11-27T13:43:35Z
dc.date2015-11-27T13:43:35Z
dc.date.accessioned2018-03-29T01:22:19Z
dc.date.available2018-03-29T01:22:19Z
dc.identifierEuropean Journal Of Medicinal Chemistry. v. 87, p. 745-58, 2014-Nov.
dc.identifier1768-3254
dc.identifier10.1016/j.ejmech.2014.09.085
dc.identifierhttp://www.ncbi.nlm.nih.gov/pubmed/25305718
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/201800
dc.identifier25305718
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1302033
dc.descriptionIn this study, a novel concise series of molecules based on the structure of goniothalamin (1) was synthesized and evaluated against a highly metastatic human pancreatic cancer cell line (Panc-1). Among them, derivative 8 displayed a low IC50 value (2.7 μM) and its concentration for decreasing colony formation was 20-fold lower than goniothalamin (1). Both compounds reduced the levels of the receptor tyrosine kinase (AXL) and cyclin D1 which are known to be overexpressed in pancreatic cancer cells. Importantly, despite the fact that goniothalamin (1) and derivative 8 caused pancreatic cancer cell cycle arrest and cell death, only derivative 8 was able to downregulate pro-survival and proliferation pathways mediated by mitogen activated protein kinase ERK1/2. Another interesting finding was that Panc-1 cells treated with derivative 8 displayed a strong decrease in the transcription factor (c-Myc), hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) protein levels. Notably, the molecular effects caused by derivative 8 might not be related to ROS generation, since no significant production of ROS was observed in low concentrations of this compound (from 1.5 up to 3 μM). Therefore, the downregulation of important mediators of pancreatic cancer aggressiveness by derivative 8 reveals its great potential for the development of new chemotherapeutic agents for pancreatic cancer treatment.
dc.description87
dc.description745-58
dc.languageeng
dc.relationEuropean Journal Of Medicinal Chemistry
dc.relationEur J Med Chem
dc.rightsfechado
dc.rightsCopyright © 2014 Elsevier Masson SAS. All rights reserved.
dc.sourcePubMed
dc.subjectAxl Kinase
dc.subjectGoniothalamin
dc.subjectHif-1α
dc.subjectN-acylated Aza-derivatives
dc.subjectPanc-1 Cells
dc.subjectPancreatic Cancer
dc.titleA New Goniothalamin N-acylated Aza-derivative Strongly Downregulates Mediators Of Signaling Transduction Associated With Pancreatic Cancer Aggressiveness.
dc.typeArtículos de revistas


Este ítem pertenece a la siguiente institución