Separate and concurrent use of 2-deoxy-D-glucose and 3-bromopyruvate in pancreatic cancer cells

Xiao,Huijie; Li,Shasha; Zhang,Dapeng; Liu,Tongjun; Yu,Ming; Wang,Feng

doi:10.3892/or.2012.2085

January 2013 Volume 29 Issue 1

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January 2013 Volume 29 Issue 1

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Article

Separate and concurrent use of 2-deoxy-D-glucose and 3-bromopyruvate in pancreatic cancer cells

Authors:
- Huijie Xiao
- Shasha Li
- Dapeng Zhang
- Tongjun Liu
- Ming Yu
- Feng Wang
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Affiliations: Department of Colorectal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China, Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, P.R. China, Institute of Chinese and Modern Medicines for Acute Abdominal Diseases, Tianjin Medical University Nankai Hospital, Tianjin 300100, P.R. China, Department of Nutrition, Tianjin Medical University School of Public Health, Tianjin 300070, P.R. China
Pages: 329-334
|
Published online on: October 17, 2012

https://doi.org/10.3892/or.2012.2085
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Abstract

Unrestrained glycolysis characterizes energy metabolism in cancer cells. Thus, antiglycolytic reagents such as 2-deoxy-D-glucose (2-DG) and 3-bromopyruvate (3-BrPA) may be used as anticancer drugs. In the present study, we examined the anticancer effects of 2-DG and 3-BrPA in pancreatic cancer cells and investigated whether these effects were regulated by hypoxia-inducible factor-1α (HIF-1α). To this end, 2-DG and 3-BrPA were administered to wild-type (wt) MiaPaCa2 and Panc-1 pancreatic cancer cells that were incubated under hypoxic (HIF-1α-positive) or normoxic (HIF-1α-negative) conditions. In addition, 2-DG and 3-BrPA were also administered to si-MiaPaCa2 and si-Panc-1 cells that lacked HIF-1α as a result of RNA interference. Following drug exposure, cell population was measured using a viability assay. Both HIF-1α-positive and HIF-1α-negative MiaPaCa2 cells were further studied for their expression of Cu/Zn-superoxide dismutase (SOD1) and poly(ADP-ribose) polymerase (PARP) and for their contents of ATP and fumarate. In the viability assay, either 2-DG or 3-BrPA decreased the tested cells. Concurrent use of 2-DG and 3-BrPA resulted in a greater decrease of cells and also facilitated ATP depletion. In addition, 3-BrPA was seen to both decrease SOD1 and increase fumarate, which suggests that the reagent impaired the mitochondria. 3-BrPA also decreased both full-length PARP and cleaved PARP, which suggests that 3-BrPA-induced decrease in cell population was a result of cell necrosis rather than apoptosis. When HIF-1α was induced in wt-MiaPaCa2 cells by hypoxia, some effects of 2-DG and 3-BrPA were attenuated. We conclude that: i) concurrent use of 2-DG and 3-BrPA has better anticancer effects in pancreatic cancer cells, ii) 3-BrPA impairs the mitochondria of pancreatic cancer cells and induces cell necrosis, and iii) HIF-1α regulates the anticancer effects of 2-DG and 3-BrPA in pancreatic cancer cells.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Separate and concurrent use of 2-deoxy-D-glucose and 3-bromopyruvate in pancreatic cancer cells

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