Targeting Warburg Effect in Cancers with PEGylated Glucose. Issue 6 (21st January 2016)

• Record Type: Journal Article
• Authors: Narayanan, Karthikeyan; Erathodiyil, Nandanan; Gopalan, Began; Chong, Shiya; Wan, Andrew C. A.; Ying, Jackie Y.
• Is Part Of: Advanced healthcare materials. Volume 5:Issue 6(2016)
• Page Start: 696
• Page End: 701
• Publication Date: 2016-01-21
• Subjects: cancer metabolism -- glucose uptake -- modified glucose -- AKT pathway -- starvation; Biomedical materials -- Periodicals; 610.28
• DOI: 10.1002/adhm.201500613
• Languages: English
• ISSNs: 2192-2640

Abstract

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. Abstract : Cancer cells heavily depend on glucose for ATP generation via glycolysis pathway. Dietary glucose restriction serves as a metabolic control of cancer cell metabolism and proliferation. PEGylated glucose treatment of cancer cells blocks the glucose transporters and inhibits the uptake of glucose, leading to metabolic arrest followed by ATP depletion. This starvation leads to apoptosis in the cancer cells.