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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Mol. Biosci. | doi: 10.3389/fmolb.2019.00090

2-Deoxyglucose and Newcastle Disease Virus synergize to Kill Breast Cancer Cells by Inhibition of Glycolysis Pathway through Glyceraldehyde3-Phosphate Downregulation

 Ahmed M. Al-Shammari, Phd1*, Amer H. Abdullah2, Zainab M. Salim2 and  Nahi Y. Yaseen1
  • 1Experimental Therapy Department, Iraqi Centre for Cancer and Medical Genetic Research, Al-Mustansiriya University, Iraq
  • 2Department of Chemistry, College of Science, Al-Mustansiriya University, Iraq

Targeting cancer cells metabolism is promising strategy in inhibiting cancer cells progression that are known to exhibit increased aerobic glycolysis. We used the glucose analog 2-Deoxyglucose (2-DG) as a competitor molecule of glucose. To further enhance the effectiveness of 2-DG, the Newcastle disease virus (NDV) was used as a combination virotherapy to enhance the anti-tumor effect. Human and mouse-breast cancer cells were treated by NDV and/or 2-DG. The effect was analyzed by study cell viability, apoptosis and level of glyceraldehyde3-phosphate (GAPDH) by ELISA and QPCR assays. Synergistic cytotoxicity was found after a 72-h treatment of human- and mouse-breast cancer cells with 2-DG in combination with NDV at different concentrations. The synergistic cytotoxicity was accompanied by apoptotic cell death and GAPDH downregulation and inhibition to glycolysis product pyruvate. The combination treatment showed significant tumor growth inhibition compared to single treatments in vivo. Our results suggest the effectiveness of a novel strategy for anti-breast cancer therapy through glycolysis inhibition and GAPDH downregulation.

Keywords: Glycolysis inhibition, virotherapy, Cancer Metabolism, Breast cancer model, Warburg effect

Received: 03 Apr 2018; Accepted: 11 Sep 2019.

Copyright: © 2019 Al-Shammari, Phd, Abdullah, Salim and Yaseen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: DVM, PhD. Ahmed M. Al-Shammari, Phd, Al-Mustansiriya University, Experimental Therapy Department, Iraqi Centre for Cancer and Medical Genetic Research, Baghdad, 1001, Iraq, ahmed.alshammari@iccmgr.org