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Cell death in response to antimetabolites directed at ribonucleotide reductase and thymidylate synthase
| Content Provider | Paperity |
|---|---|
| Author | Jonathan, R. Aspe Jonathan, W. Neidigh Gonda, Amber Carlos, J. Diaz Osterman Castro, Imilce Malyn, M. Asuncion Valenzuela Khan, Salma Jessica, M. Jutzy Nathan, R. Wall |
| Abstract | Cell death in response to antimetabolites directed at ribonucleotide reductase and thymidylate synthase Malyn M Asuncion Valenzuela, Imilce Castro, Amber Gonda, Carlos J Diaz Osterman, Jessica M Jutzy, Jonathan R Aspe, Salma Khan, Jonathan W Neidigh, Nathan R Wall Center for Health Disparities and Molecular Medicine, Division of Biochemistry, Department of Basic Sciences, Loma Linda University, Loma Linda, CA, USA Abstract: New agent development, mechanistic understanding, and combinatorial partnerships with known and novel modalities continue to be important in the study of pancreatic cancer and its improved treatment. In this study, known antimetabolite drugs such as gemcitabine (ribonucleotide reductase inhibitor) and 5-fluorouracil (thymidylate synthase inhibitor) were compared with novel members of these two drug families in the treatment of a chemoresistant pancreatic cancer cell line PANC-1. Cellular survival data, along with protein and messenger ribonucleic acid expression for survivin, XIAP, cIAP1, and cIAP2, were compared from both the cell cytoplasm and from exosomes after single modality treatment. While all antimetabolite drugs killed PANC-1 cells in a time- and dose-dependent manner, neither family significantly altered the cytosolic protein level of the four inhibitors of apoptosis (IAPs) investigated. Survivin, XIAP, cIAP1, and cIAP2 were found localized to exosomes where no significant difference in expression was recorded. This inability for significant and long-lasting expression may be a reason why pancreatic cancer lacks responsiveness to these and other cancer-killing agents. Continued investigation is required to determine the responsibilities of these IAPs in their role in chemoresistance in pancreatic adenocarcinoma. Keywords: IAPs, exosomes, pancreatic cancer, antimetabolites, gemcitabine, cladribine, hydroxyurea, 5-fluorodeoxyuridine, 5-fluorouracil |
| Starting Page | 495 |
| Ending Page | 507 |
| File Format | HTM / HTML |
| DOI | 10.2147/OTT.S79647 |
| Journal | OncoTargets and Therapy |
| e-ISSN | 11786930 |
| Language | English |
| Publisher | Dove Medical Press |
| Publisher Date | 2015-02-26 |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
