Oxidative Stress Therapy for Cancer Using Glycolysis Inhibitors: Towards Improving Therapeutic Outcomes

Salah Mohamed El Sayed^{1, 2,}

¹Department of Clinical Biochemistry and Molecular Medicine, Taibah College of Medicine, Taibah University, Al-Madinah Al-Munawwarah, Saudi Arabia

²Department of Medical Biochemistry, Sohag Faculty of Medicine, Sohag University, Egypt

Cite this paper

Salah Mohamed El Sayed. Oxidative Stress Therapy for Cancer Using Glycolysis Inhibitors: Towards Improving Therapeutic Outcomes. American Journal of Medical and Biological Research. 2018; 6(1):11-15. doi: 10.12691/AJMBR-6-1-3

Abstract

Cancer cure is still a big challenge despite intensive conventional treatment. Unfortunately, many unsolved problems e.g. metastasis and drug resistance still exist. Better understanding of cancer biology to identify important differences between cancer cells and normal cells seems vital to improve cancer treatment. Tumors depend on glycolysis for energy production, exhibit Warburg effect, establish aggressive microenvironment, have low antioxidant systems and are under high steady-state ROS conditions. Normal cells differ in all of that. Lactate produced through Warburg effect maintains the high steady-state ROS condition in cancer cells and helps cancer cells to metastasize and establish their hostile microenvironment. Cancer cells seem sensitive to oxidative stress therapy using ROS generating chemotherapy e.g. 3-bromopyruvate (3BP). 3BP is a powerful antiglycolytic that may be more promising as a potent anticancer if it is conjugated with polyethylene glycol (PEG). Targeting glycolysis in cancer cells seems promising in decreasing their survival and metastasis. Glycolysis double inhibition by combination of multiple antiglycolytics e.g. 3BP with citrate was synergistic in cancer treatment. Being analog to pyruvate and lactate, 3BP antagonized Warburg effect, antagonized effects of pyruvate and lactate, improved sensitivity of chemoresistant cancer cells and targeted cancer cell survival, migration and metastasis. In this review, I discuss 3BP-induced oxidative stress and ATP depletion as a promising treatment modality for cancer.

Keywords

3-bromopyruvate, EPR effect, PEG formulation, glycolysis, citrate

Copyright

This work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

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