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

Autor:	Majid S. Jabir, Ahmed Majeed Al-Shammari, Haider Sabah Kadhim, Mohammed I. Hamzah, Ahmed Ghdhban Al-Ziaydi
Jazyk:	angličtina
Rok vydání:	2020
Předmět:	Oncolytic Newcastle Disease Virus Pyruvate Cancer Research Cytotoxicity lcsh:RC254-282 03 medical and health sciences Glycolysis Inhibition chemistry.chemical_compound 0302 clinical medicine Genetics Glycolysis lcsh:QH573-671 030304 developmental biology 0303 health sciences Hexokinase Cell growth lcsh:Cytology Anticancer therapy lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Warburg effect Oncology chemistry Hexokinase inhibitor 030220 oncology & carcinogenesis Cancer cell Cancer research Mannoheptulose Primary Research
Zdroj:	Cancer Cell International, Vol 20, Iss 1, Pp 1-10 (2020) Cancer Cell International
ISSN:	1475-2867
DOI:	10.1186/s12935-020-01514-2
Popis:	Background 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. Methods 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. Results 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. Conclusions 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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b1e7cc30c5fa73a6e01cca2e21500162 http://link.springer.com/article/10.1186/s12935-020-01514-2 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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