Cell death in response to antimetabolites directed at ribonucleotide reductase and thymidylate synthase

OncoTargets and Therapy
Malyn M Asuncion ValenzuelaNathan R Wall

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 ...Continue Reading

Citations

May 20, 2015·Cancer Microenvironment : Official Journal of the International Cancer Microenvironment Society·Malyn May Asuncion ValenzuelaNathan R Wall
Jun 30, 2015·Cancer Letters·Changqing Su

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Methods Mentioned

BETA
protein assay
PCR
Assay

Software Mentioned

GraphPad Prism
FlowJo
ExoQuick

Related Concepts

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis