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Experimental Hematology & Oncology
Published in: Experimental Hematology & Oncology 1/2013

Open Access 01-12-2013 | Research

Inhibition of transketolase by oxythiamine altered dynamics of protein signals in pancreatic cancer cells

Authors: Jiarui Wang, Xuemei Zhang, Danjun Ma, Wai-Nang Paul Lee, Jing Xiao, Yingchun Zhao, Vay Liang Go, Qi Wang, Yun Yen, Robert Recker, Gary Guishan Xiao

Published in: Experimental Hematology & Oncology | Issue 1/2013

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Abstract

Oxythiamine (OT), an analogue of anti-metabolite, can suppress the nonoxidative synthesis of ribose and induce cell apoptosis by causing a G1 phase arrest in vitro and in vivo. However, the molecular mechanism remains unclear yet. In the present study, a quantitative proteomic analysis using the modified SILAC method (mSILAC) was performed to determine the effect of metabolic inhibition on dynamic changes of protein expression in MIA PaCa-2 cancer cells treated with OT at various doses (0 μM, 5 μM, 50 μM and 500 μM) and time points (0 h, 12 h and 48 h). A total of 52 differential proteins in MIA PaCa-2 cells treated with OT were identified, including 14 phosphorylated proteins. Based on the dynamic expression pattern, these proteins were categorized in three clusters, straight down-regulation (cluster 1, 37% of total proteins), upright “V” shape expression pattern (cluster 2, 47.8% total), and downright “V” shape pattern (cluster 3, 15.2% total). Among them, Annexin A1 expression was significantly down-regulated by OT treatment in time-dependent manner, while no change of this protein was observed in OT dose-dependent fashion. Pathway analysis suggested that inhibition of transketolase resulted in changes of multiple cellular signaling pathways associated with cell apoptosis. The temporal expression patterns of proteins revealed that OT altered dynamics of protein expression in time-dependent fashion by suppressing phosphor kinase expression, resulting in cancer cell apoptosis. Results from this study suggest that interference of single metabolic enzyme activity altered multiple cellular signaling pathways.
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Metadata
Title
Inhibition of transketolase by oxythiamine altered dynamics of protein signals in pancreatic cancer cells
Authors
Jiarui Wang
Xuemei Zhang
Danjun Ma
Wai-Nang Paul Lee
Jing Xiao
Yingchun Zhao
Vay Liang Go
Qi Wang
Yun Yen
Robert Recker
Gary Guishan Xiao
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Experimental Hematology & Oncology / Issue 1/2013
Electronic ISSN: 2162-3619
DOI
https://doi.org/10.1186/2162-3619-2-18

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