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Separate and concurrent use of 2-deoxy-D-glucose and 3-bromopyruvate in pancreatic cancer cells
- Source :
- Oncology Reports. 29:329-334
- Publication Year :
- 2012
- Publisher :
- Spandidos Publications, 2012.
-
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.
- 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
Subjects
Details
- ISSN :
- 17912431 and 1021335X
- Volume :
- 29
- Database :
- OpenAIRE
- Journal :
- Oncology Reports
- Accession number :
- edsair.doi.dedup.....9415c6c6975a69d1329fdfa0e05fe4ac