Hexokinase inhibition using D-Mannoheptulose enhances oncolytic newcastle disease virus-mediated killing of breast cancer cells

• Published in: Cancer cell international Vol. 20; no. 1; p. 420
• Main Authors: Al-Ziaydi, Ahmed Ghdhban, Al-Shammari, Ahmed Majeed, Hamzah, Mohammed I, Kadhim, Haider Sabah, Jabir, Majid Sakhi
• Format: Journal Article
• Language: English
• Published: England BioMed Central 28.08.2020; BMC
• Subjects: Acidity; Anticancer therapy; Apoptosis; Breast cancer; Cell culture; Cell death; Cell proliferation; Cell viability; Cytotoxicity; Enzymes; Glucose; Glycolysis; Hexokinase; Hexokinase inhibitor; Immunotherapy; Kinases; Medical prognosis; Metabolic pathways; Metabolism; Newcastle disease; Oncolysis; Primary Research; Pyruvate; Pyruvic acid; Stains & staining; Warburg effect; Baghdad Iraq; Iraq; United States > US; Germany; Pyruvate; Cytotoxicity; Hexokinase inhibitor; Anticancer therapy; Warburg effect
• ISSN: 1475-2867; 1475-2867
• DOI: 10.1186/s12935-020-01514-2

Most cancer cells exhibit increased glycolysis and use this metabolic pathway cell growth and proliferation. Targeting cancer cells' metabolism is a promising strategy in inhibiting cancer cell progression. We used D-Mannoheptulose, a specific hexokinase inhibitor, to inhibit glycolysis to enhance the Newcastle disease virus anti-tumor effect. Human breast cancer cells were treated by NDV and/or hexokinase inhibitor. The study included cell viability, apoptosis, and study levels of hexokinase enzyme, pyruvate, ATP, and acidity. The combination index was measured to determine the synergism of NDV and hexokinase inhibitor. The results showed synergistic cytotoxicity against breast cancer cells by combination therapy but no cytotoxic effect against normal cells. The effect was accompanied by apoptotic cell death and hexokinase downregulation and inhibition to glycolysis products, pyruvate, ATP, and acidity. The combination treatment showed safe significant tumor cell proliferation inhibition compared to monotherapies suggesting a novel strategy for anti-breast cancer therapy through glycolysis inhibition by hexokinase downregulation.