1. Separate and concurrent use of 2-deoxy-D-glucose and 3-bromopyruvate in pancreatic cancer cells
- Author
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Tongjun Liu, Huijie Xiao, Shasha Li, Dapeng Zhang, Feng Wang, and Ming Yu
- Subjects
Cancer Research ,Antimetabolites ,Blotting, Western ,Cell ,Apoptosis ,Pyruvate Dehydrogenase Complex ,Deoxyglucose ,Biology ,medicine.disease_cause ,Adenosine Triphosphate ,Fumarates ,Pancreatic cancer ,Antineoplastic Combined Chemotherapy Protocols ,Tumor Cells, Cultured ,medicine ,Humans ,Viability assay ,Enzyme Inhibitors ,RNA, Small Interfering ,Pyruvates ,Cell Proliferation ,Superoxide Dismutase ,Cancer ,Drug Synergism ,General Medicine ,Cell cycle ,Hypoxia-Inducible Factor 1, alpha Subunit ,medicine.disease ,Cell Hypoxia ,Mitochondria ,Pancreatic Neoplasms ,medicine.anatomical_structure ,Oncology ,Cancer cell ,Cancer research ,Poly(ADP-ribose) Polymerases ,Carcinogenesis - Abstract
Unrestrained glycolysis characterizes energy meta-bolism 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.
- Published
- 2012