Cell lines

Cell lines SkBr3, MCF-7, BT474, and MDA/MB468,

Preparation Method

Cells were plated at 4000 cells well-1 in a 96-well plate, allowed 24 h to attach and subsequently exposed for 4 days to 2-Deoxy-D-glucose.

Reaction Conditions

4-12 mM for 0-4 days

Applications

Growth of MDA/MB468 cells was completely inhibited by treatment with 8 mM 2-Deoxy-D-glucose. Treatment with 4 mM 2-Deoxy-D-glucose resulted in approximately 30% inhibition of cell growth. Of the breast cancer cell lines tested, SkBr3 was the most sensitive to the growth inhibitory effects of 2-Deoxy-D-glucose. Cell growth was completely inhibited at 4 mM 2-Deoxy-D-glucose.

Animal models

male Sprague-Dawley (SD) rats

Preparation Method

Animals were handled routinely in order to reduce stress associated with injection. 2-deoxy-d-glucose (400 mg/kg), or saline, was administered intraperitoneally.

Dosage form

Intraperitoneal injection , 400 mg/kg

Applications

Ad concentrations increased from 2.73 ng/ml to 7.2 ng/ml while NAd concentrations increased from 1.8 ng/ml to 3.14 ng/ml after injected 2-deoxy-d-glucose.

• The FASEB Journal (2020). PMID:33184921
• Cell Death Dis 11.11 (2020): 1-23. PMID:33203874

2-Deoxy-D-glucose (2DG), is a glucose analogue, act as competitive glycolytic inhibitor^[1].

2-Deoxy-d-glucose (2DG) has been demonstrated to be a powerful agent for blocking and probing increased sugar metabolism in cancer cells^[2]. Because of its similarity to glucose, 2-Deoxy-D-glucose inhibits glycolysis, but as chemically it is also 2-deoxymannose it is able to compete with mannose in the growing lipid-linked oligosaccharide chain during the initial steps of N-linked glycosylation. This mannose-like property of 2-Deoxy-D-glucose results in misfolded proteins leading to endoplasmic reticulum (ER) stress^[3].

2-Deoxy-D-glucose delivered in the diet produces cardiac toxicity in rats at doses ranging from 0.02 to 0.3 g/kg (0.04-0.6% 2-Deoxy-D-glucose by weight in the diet) and hastens mortality at doses above 0.2 g/kg (0.4% in the diet)^[4]. 2-Deoxy-D-glucose evoked increases in plasma adrenaline and glucose at 20 and 60 min^[5].

References:
[1]. MUhlenberg T, Grunewald S, Treckmann J, et al. Inhibition of KIT-glycosylation by 2-deoxyglucose abrogates KIT-signaling and combination with ABT-263 synergistically induces apoptosis in gastrointestinal stromal tumor[J]. PloS one, 2015, 10(3): e0120531.
[2]. El Mjiyad N, Caro-Maldonado A, Ramirez-Peinado S, Munoz-Pinedo C. Sugar-free approaches to cancer cell killing. Oncogene. 2011 Jan;30(3):253-64.
[3]. Kurtoglu, Metin, Johnathan C. Maher, and Theodore J. Lampidis. "Differential toxic mechanisms of 2-deoxy-D-glucose versus 2-fluorodeoxy-D-glucose in hypoxic and normoxic tumor cells." Antioxidants & redox signaling 9.9 (2007): 1383-1390.
[4]. Minor R K, Smith Jr D L, Sossong A M, et al. Chronic ingestion of 2-deoxy-D-glucose induces cardiac vacuolization and increases mortality in rats[J]. Toxicology and applied pharmacology, 2010, 243(3): 332-339.
[5]. Bobrovskaya L, Damanhuri H A, Ong L K, et al. Signal transduction pathways and tyrosine hydroxylase regulation in the adrenal medulla following glucoprivation: an in vivo analysis[J]. Neurochemistry international, 2010, 57(2): 162-167.