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Cancers
Volume 12
Issue 7
10.3390/cancers12071814
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Article

Human Prostate Cancer Is Characterized by an Increase in Urea Cycle Metabolites

by
Andras Franko
1,2,3,†,
Yaping Shao
4,†,
Martin Heni
1,2,3,
Jörg Hennenlotter
5,
Miriam Hoene
6,
Chunxiu Hu
4,
Xinyu Liu
4,
Xinjie Zhao
4,
Qingqing Wang
4,
Andreas L. Birkenfeld
1,2,3,
Tilman Todenhöfer
5,
Arnulf Stenzl
5,
Andreas Peter
6,
Hans-Ulrich Häring
1,2,3,
Rainer Lehmann
2,3,6,*,
Guowang Xu
4,* and
Stefan Z. Lutz
1,7
1
Department of Internal Medicine, Division of Endocrinology, Diabetology and Nephrology, University Hospital Tübingen, 72076 Tübingen, Germany
2
Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, 72076 Tübingen, Germany
3
German Center for Diabetes Research (DZD), 72076 Tübingen, Germany
4
CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China
5
Department of Urology, University Hospital Tübingen, 72076 Tübingen, Germany
6
Institute for Clinical Chemistry and Pathobiochemistry, Department for Diagnostic Laboratory Medicine, University Hospital Tübingen, 72076 Tübingen, Germany
7
Clinic for Geriatric and Orthopedic Rehabilitation Bad Sebastiansweiler, 72116 Mössingen, Germany
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Cancers 2020, 12(7), 1814; https://doi.org/10.3390/cancers12071814
Received: 28 May 2020 / Revised: 30 June 2020 / Accepted: 1 July 2020 / Published: 6 July 2020
(This article belongs to the Special Issue Tumor Metabolome: Therapeutic Opportunities Targeting Cancer Metabolic Reprogramming)
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Abstract

Despite it being the most common incident of cancer among men, the pathophysiological mechanisms contributing to prostate cancer (PCa) are still poorly understood. Altered mitochondrial metabolism is postulated to play a role in the development of PCa. To determine the key metabolites (which included mitochondrial oncometabolites), benign prostatic and cancer tissues of patients with PCa were analyzed using capillary electrophoresis and liquid chromatography coupled with mass spectrometry. Gene expression was studied using real-time PCR. In PCa tissues, we found reduced levels of early tricarboxylic acid cycle metabolites, whereas the contents of urea cycle metabolites including aspartate, argininosuccinate, arginine, proline, and the oncometabolite fumarate were higher than that in benign controls. Fumarate content correlated positively with the gene expression of oncogenic HIF1α and NFκB pathways, which were significantly higher in the PCa samples than in the benign controls. Furthermore, data from the TCGA database demonstrated that prostate cancer patients with activated NFκB pathway had a lower survival rate. In summary, our data showed that fumarate content was positively associated with carcinogenic genes. View Full-Text
Keywords: prostate cancer; metabolomics; urea cycle; fumarate; oncometabolite; NFκB prostate cancer; metabolomics; urea cycle; fumarate; oncometabolite; NFκB
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Franko, A.; Shao, Y.; Heni, M.; Hennenlotter, J.; Hoene, M.; Hu, C.; Liu, X.; Zhao, X.; Wang, Q.; Birkenfeld, A.L.; Todenhöfer, T.; Stenzl, A.; Peter, A.; Häring, H.-U.; Lehmann, R.; Xu, G.; Lutz, S.Z. Human Prostate Cancer Is Characterized by an Increase in Urea Cycle Metabolites. Cancers 2020, 12, 1814. https://doi.org/10.3390/cancers12071814

AMA Style

Franko A, Shao Y, Heni M, Hennenlotter J, Hoene M, Hu C, Liu X, Zhao X, Wang Q, Birkenfeld AL, Todenhöfer T, Stenzl A, Peter A, Häring H-U, Lehmann R, Xu G, Lutz SZ. Human Prostate Cancer Is Characterized by an Increase in Urea Cycle Metabolites. Cancers. 2020; 12(7):1814. https://doi.org/10.3390/cancers12071814

Chicago/Turabian Style

Franko, Andras, Yaping Shao, Martin Heni, Jörg Hennenlotter, Miriam Hoene, Chunxiu Hu, Xinyu Liu, Xinjie Zhao, Qingqing Wang, Andreas L. Birkenfeld, Tilman Todenhöfer, Arnulf Stenzl, Andreas Peter, Hans-Ulrich Häring, Rainer Lehmann, Guowang Xu, and Stefan Z. Lutz. 2020. "Human Prostate Cancer Is Characterized by an Increase in Urea Cycle Metabolites" Cancers 12, no. 7: 1814. https://doi.org/10.3390/cancers12071814

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