Targeting Warburg Effect in Cancers with PEGylated Glucose
| Autor: | Began Gopalan, Nandanan Erathodiyil, Shiya Chong, Karthikeyan Narayanan, Andrew C.A. Wan, Jackie Y. Ying |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Glucose uptake Blotting Western Transplantation Heterologous Biomedical Engineering Pharmaceutical Science Antineoplastic Agents Apoptosis Mice SCID Biology Polyethylene Glycols Biomaterials Mice 03 medical and health sciences Cell Line Tumor Neoplasms Internal medicine medicine Animals Humans Glycolysis Cell Proliferation Fluorescent Dyes Glucose Transporter Type 1 Caspase 3 Cell growth Glucose transporter Hep G2 Cells Warburg effect Disease Models Animal Glucose 030104 developmental biology Endocrinology Microscopy Fluorescence Cancer cell Toxicity MCF-7 Cells Proto-Oncogene Proteins c-akt |
| Zdroj: | Advanced Healthcare Materials. 5:696-701 |
| ISSN: | 2192-2640 |
| DOI: | 10.1002/adhm.201500613 |
| Popis: | In highly proliferative cancer cells, energy is predominantly produced by a high rate of glycolysis, followed by lactic acid fermentation, despite the availability of oxygen - an observation known as the Warburg effect. As a consequence, cells employing this glycolytic pathway require high uptake of glucose and increased metabolic rates to maintain their proliferation. It has been hypothesized that by blocking glucose uptake using modified glucose molecules, apoptosis in the cancer cells can be induced. In this study, it has been showed that several poly(ethylene glycol) (PEG)-modified glucose compounds could reduce cell proliferation in various cancer cell lines by a phenomenon that blocked the availability of the glucose transporters and reduced AKT1 (serine/threonine-specific protein kinase) activation. Xenograft cancer models that are intravenously administered with glucose-conjugated branched PEG (GBrP) daily for 14 d show little tumor development, as compared to the control group without GBrP treatment. The toxicological effects and the pharmacokinetics of the PEGylated glucose are studied in rodents. The PEGylated glucose exerts no systemic toxicity at 40 mg kg(-1) dosage. However, doses above 80 mg kg(-1) show dose-dependent toxicity in all the organs analyzed. The present results suggest PEGylated glucose as a promising "metabolic therapy" approach for the treatment of cancer. |
| Databáze: | OpenAIRE |
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