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Targeting Cellular Metabolism Chemosensitizes the Doxorubicin-Resistant Human Breast Adenocarcinoma Cells

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Journal Biomed Res Int
Publisher Wiley
Date 2015 Nov 12
PMID 26558272
Citations 18
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Abstract

Metabolic energy preferentially produced by glycolysis was an advantageous metabolic phenotype of cancer cells. It is also an essential contributor to the progression of multidrug resistance in cancer cells. By developing human breast cancer MCF-7 cells resistant to doxorubicin (DOX) (MCF-7/MDR cells), the effects and mechanisms of 2-deoxy-D-glucose (2DG), a glucose analogue, on reversing multidrug resistance were investigated. 2DG significantly inhibited the viability of MCF-7/MDR cells and enhanced DOX-induced apoptosis by upregulating protein expression of AMPKα, P53, and caspase-3. The study demonstrated that energy restriction induced by 2DG was relevant to the synergistic effect of 2DG and DOX. The proteins of multidrug gene (the MDR-related protein, MRP1) and P-glycoprotein (P-gp) in MCF-7/MDR cells were downregulated after exposure to 2DG, accompanied with the suppression of the activity of ATP-dependent drug-efflux pump and transmembrane transporter, increasing the intracellular accumulation of DOX to reverse the chemoresistance in multidrug cancer cells.

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References
1.
Vander Heiden M, Cantley L, Thompson C . Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science. 2009; 324(5930):1029-33. PMC: 2849637. DOI: 10.1126/science.1160809. View

2.
Kroemer G, Pouyssegur J . Tumor cell metabolism: cancer's Achilles' heel. Cancer Cell. 2008; 13(6):472-82. DOI: 10.1016/j.ccr.2008.05.005. View

3.
Tang C, Wu W, Tsai S, Yoshinaga T, Lee T . Elevated Na+/K+-ATPase responses and its potential role in triggering ion reabsorption in kidneys for homeostasis of marine euryhaline milkfish (Chanos chanos) when acclimated to hypotonic fresh water. J Comp Physiol B. 2010; 180(6):813-24. DOI: 10.1007/s00360-010-0458-x. View

4.
Wolf A, Agnihotri S, Micallef J, Mukherjee J, Sabha N, Cairns R . Hexokinase 2 is a key mediator of aerobic glycolysis and promotes tumor growth in human glioblastoma multiforme. J Exp Med. 2011; 208(2):313-26. PMC: 3039857. DOI: 10.1084/jem.20101470. View

5.
Martinez-Outschoorn U, Lin Z, Ko Y, Goldberg A, Flomenberg N, Wang C . Understanding the metabolic basis of drug resistance: therapeutic induction of the Warburg effect kills cancer cells. Cell Cycle. 2011; 10(15):2521-8. PMC: 3180190. DOI: 10.4161/cc.10.15.16584. View