title: Targeting Warburg Effect in Cancers with PEGylated Glucose.
abstract: 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.
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore, 138669, Singapore.
authors.forename: Karthikeyan
authors.initials: K
authors.lastname: Narayanan
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore, 138669, Singapore.
authors.forename: Nandanan
authors.initials: N
authors.lastname: Erathodiyil
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore, 138669, Singapore.
authors.forename: Began
authors.initials: B
authors.lastname: Gopalan
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore, 138669, Singapore.
authors.forename: Shiya
authors.initials: S
authors.lastname: Chong
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore, 138669, Singapore.
authors.forename: Andrew C A
authors.initials: AC
authors.lastname: Wan
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore, 138669, Singapore.
authors.forename: Jackie Y
authors.initials: JY
authors.lastname: Ying
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D005456:Fluorescent Dyes / Q000737:chemistry; D005947:Glucose / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D051272:Glucose Transporter Type 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D016513:Mice, SCID; D008856:Microscopy, Fluorescence; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D011092:Polyethylene Glycols / Q000737:chemistry*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D014183:Transplantation, Heterologous
chemical_list: D000970:Antineoplastic Agents; D005456:Fluorescent Dyes; D051272:Glucose Transporter Type 1; D011092:Polyethylene Glycols; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3; D005947:Glucose
keywords: AKT pathway; cancer metabolism; glucose uptake; modified glucose; starvation