Version 1
: Received: 10 May 2024 / Approved: 13 May 2024 / Online: 13 May 2024 (12:21:07 CEST)
How to cite:
Zhou, Q.; Nguyen, T. T. T.; Mun, J.-Y.; Siegelin, M. D.; Greene, L. A. DPEP Inhibits Cancer Cell Glucose Uptake, Glycolysis and Survival by Upregulating Tumor Suppressor TXNIP. Preprints2024, 2024050846. https://doi.org/10.20944/preprints202405.0846.v1
Zhou, Q.; Nguyen, T. T. T.; Mun, J.-Y.; Siegelin, M. D.; Greene, L. A. DPEP Inhibits Cancer Cell Glucose Uptake, Glycolysis and Survival by Upregulating Tumor Suppressor TXNIP. Preprints 2024, 2024050846. https://doi.org/10.20944/preprints202405.0846.v1
Zhou, Q.; Nguyen, T. T. T.; Mun, J.-Y.; Siegelin, M. D.; Greene, L. A. DPEP Inhibits Cancer Cell Glucose Uptake, Glycolysis and Survival by Upregulating Tumor Suppressor TXNIP. Preprints2024, 2024050846. https://doi.org/10.20944/preprints202405.0846.v1
APA Style
Zhou, Q., Nguyen, T. T. T., Mun, J. Y., Siegelin, M. D., & Greene, L. A. (2024). DPEP Inhibits Cancer Cell Glucose Uptake, Glycolysis and Survival by Upregulating Tumor Suppressor TXNIP. Preprints. https://doi.org/10.20944/preprints202405.0846.v1
Chicago/Turabian Style
Zhou, Q., Markus D Siegelin and Lloyd A Greene. 2024 "DPEP Inhibits Cancer Cell Glucose Uptake, Glycolysis and Survival by Upregulating Tumor Suppressor TXNIP" Preprints. https://doi.org/10.20944/preprints202405.0846.v1
Abstract
We have designed cell penetrating peptides that target the leucine zipper transcription factors ATF5, CE-BPB and CEBPD and that promote apoptotic death of a wide range of cancer cell types, but not normal cells, in vitro and in vivo. While such peptides have the potential for clinical application, their mechanisms of action are not fully understood. Here, we show that one such peptide, Dpep, compromises glucose uptake and glycolysis in a cell-context-dependent manner (in about 2/3 of cancer lines assessed). These actions are dependent on induction of tumor suppressor TXNIP (thioredoxin interacting protein) mRNA and protein. Knockdown studies show that TXNIP significantly contributes to apoptotic death in those cancer cells in which it is induced by Dpep. The metabolic actions of Dpep on glycolysis led us to explore combinations of Dpep with clinically approved drugs metformin and atovaquone that inhibit oxidative phosphorylation and that are in trials for cancer treatment. Dpep showed additive to synergistic activities in all lines tested. In summary, we find that Dpep induces TXNIP in a cell-context-dependent manner that in turn sup-presses glucose uptake and glycolysis and contributes to apoptotic death of a range of cancer cells.
Medicine and Pharmacology, Oncology and Oncogenics
Copyright:
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.
