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

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 mod...

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Autores principales: Wang, Jiarui, Zhang, Xuemei, Ma, Danjun, Lee, Wai-Nang Paul, Xiao, Jing, Zhao, Yingchun, Go, Vay Liang, Wang, Qi, Yen, Yun, Recker, Robert, Xiao, Gary Guishan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3733980/
https://www.ncbi.nlm.nih.gov/pubmed/23890079
http://dx.doi.org/10.1186/2162-3619-2-18
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author Wang, Jiarui
Zhang, Xuemei
Ma, Danjun
Lee, Wai-Nang Paul
Xiao, Jing
Zhao, Yingchun
Go, Vay Liang
Wang, Qi
Yen, Yun
Recker, Robert
Xiao, Gary Guishan
author_facet Wang, Jiarui
Zhang, Xuemei
Ma, Danjun
Lee, Wai-Nang Paul
Xiao, Jing
Zhao, Yingchun
Go, Vay Liang
Wang, Qi
Yen, Yun
Recker, Robert
Xiao, Gary Guishan
author_sort Wang, Jiarui
collection PubMed
description 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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spelling pubmed-37339802013-08-06 Inhibition of transketolase by oxythiamine altered dynamics of protein signals in pancreatic cancer cells Wang, Jiarui Zhang, Xuemei Ma, Danjun Lee, Wai-Nang Paul Xiao, Jing Zhao, Yingchun Go, Vay Liang Wang, Qi Yen, Yun Recker, Robert Xiao, Gary Guishan Exp Hematol Oncol Research 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. BioMed Central 2013-07-27 /pmc/articles/PMC3733980/ /pubmed/23890079 http://dx.doi.org/10.1186/2162-3619-2-18 Text en Copyright © 2013 Wang et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Wang, Jiarui
Zhang, Xuemei
Ma, Danjun
Lee, Wai-Nang Paul
Xiao, Jing
Zhao, Yingchun
Go, Vay Liang
Wang, Qi
Yen, Yun
Recker, Robert
Xiao, Gary Guishan
Inhibition of transketolase by oxythiamine altered dynamics of protein signals in pancreatic cancer cells
title Inhibition of transketolase by oxythiamine altered dynamics of protein signals in pancreatic cancer cells
title_full Inhibition of transketolase by oxythiamine altered dynamics of protein signals in pancreatic cancer cells
title_fullStr Inhibition of transketolase by oxythiamine altered dynamics of protein signals in pancreatic cancer cells
title_full_unstemmed Inhibition of transketolase by oxythiamine altered dynamics of protein signals in pancreatic cancer cells
title_short Inhibition of transketolase by oxythiamine altered dynamics of protein signals in pancreatic cancer cells
title_sort inhibition of transketolase by oxythiamine altered dynamics of protein signals in pancreatic cancer cells
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3733980/
https://www.ncbi.nlm.nih.gov/pubmed/23890079
http://dx.doi.org/10.1186/2162-3619-2-18
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