The anti-tumor efficacy of 2-deoxyglucose and D-allose are enhanced with p38 inhibition in pancreatic and ovarian cell lines

Autor: Liliana Carbajal, Amanda F. Baker, Neale T. Hanke, Scott W. Malm, Alexander Gill
Jazyk: angličtina
Rok vydání: 2015
Předmět:
MAPK/ERK pathway
Cancer Research
p38 mitogen activated protein kinase
endocrine system diseases
Transcription
Genetic
Pyridines
Antineoplastic Agents
Biology
Deoxyglucose
Hypoxia inducible factor 1α
p38 Mitogen-Activated Protein Kinases
03 medical and health sciences
0302 clinical medicine
Western blot
Ovarian cancer
Genes
Reporter
Cell Line
Tumor
D-allose
medicine
Humans
MTT assay
Lactic Acid
Protein kinase A
030304 developmental biology
Cell Proliferation
Cisplatin
Ovarian Neoplasms
0303 health sciences
medicine.diagnostic_test
Dose-Response Relationship
Drug
Cell growth
Imidazoles
Pancreatic cancer
Hypoxia-Inducible Factor 1
alpha Subunit
Molecular biology
Cell Hypoxia
3. Good health
2-deoxy-glucose
Pancreatic Neoplasms
Glucose
Oncology
Cell culture
Apoptosis
030220 oncology & carcinogenesis
Female
Poly(ADP-ribose) Polymerases
medicine.drug
Research Article
Zdroj: Journal of Experimental & Clinical Cancer Research : CR
ISSN: 1756-9966
0392-9078
Popis: Purpose The anti-tumor activity of glucose analogs 2-deoxy-glucose (2-DG) and D-allose was investigated alone or in combination with p38 mitogen-activated protein kinase (MAPK) inhibitor SB202190 or platinum analogs as a strategy to pharmacologically target glycolytic tumor phenotypes. Methods Hypoxia inducible factor-1 alpha (HIF-1α) protein accumulation in pancreatic cell lines treated with SB202190 alone and in combination with glucose analogs was analyzed by Western blot. HIF-1α transcriptional activity was measured in MIA PaCa-2 cells stably transfected with a hypoxia response element luciferase reporter following treatment with glucose analogs alone, and in combination with SB202190. Induction of cleaved poly(ADP-ribose) polymerase (PARP) was measured by Western blot in the MIA PaCa-2 cells. In vitro anti-proliferative activity of 2-DG and D-allose alone, or in combination with oxaliplatin (pancreatic cell lines), cisplatin (ovarian cell lines), or with SB202190 were investigated using the MTT assay. Results SB202190 decreased HIF-1α protein accumulation and transcriptional activity. 2-DG demonstrated greater anti-proliferative activity than D-allose. Pre-treatment with SB202190 enhanced activity of both 2-DG and D-allose in MIA PaCa-2, BxPC-3, ASPC-1, and SK-OV-3 cells. The combination of D-allose and platinum agents was additive to moderately synergistic in all but the OVCAR-3 and HEY cells. SB202190 pre-treatment further enhanced activity of D-allose and 2-DG with platinum agents in most cell lines investigated. Conclusions SB202190 induced sensitization of tumor cells to 2-DG and D-allose may be partially mediated by inhibition of HIF-1α activity. Combining glucose analogs and p38 MAPK inhibitors with chemotherapy may be an effective approach to target glycolytic tumor phenotypes.
Databáze: OpenAIRE
Externí odkaz: