Casiopeina II-gly and bromo-pyruvate inhibition of tumor hexokinase, glycolysis, and oxidative phosphorylation

Archives of Toxicology
Alvaro Marín-HernándezSara Rodríguez-Enríquez

Abstract

The copper-based drug Casiopeina II-gly (CasII-gly) shows potent antineoplastic effect and diminishes mitochondrial metabolism on several human and rodent malignant tumors. To elucidate whether CasII-gly also affects glycolysis, (a) the flux through the complete pathway and the initial segment and (b) the activities of several glycolytic enzymes of AS-30D hepatocarcinoma cells were determined. CasII-gly (IC₅₀ = 0.74-6.7 μM) was more effective to inhibit 24-72 h growth of several human carcinomas than 3-bromopyruvate (3BrPyr) (IC₅₀ = 45-100 μM) with no apparent effect on normal human-proliferating lymphocytes and HUVECs. In short-term 60-min experiments, CasII-gly increased tumor cell lactate production and glycogen breakdown. CasII-gly was 1.3-21 times more potent than 3BrPyr and cisplatin to inhibit tumor HK. As CasII-gly inhibited the soluble and mitochondrial HK activities and the flux through the HK-TPI glycolytic segment, whereas PFK-1, GAPDH, PGK, PYK activities and HPI-TPI segment flux were not affected, the data suggested glycogenolysis activation induced by HK inhibition. Accordingly, glycogen-depleted as well as oligomycin-treated cancer cells became more sensitive to CasII-gly. The inhibition time-course of HK by Cas...Continue Reading

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Citations

Feb 6, 2013·PloS One·Alejandra Idan Valencia-CruzCarmen Mejía
May 6, 2014·Archives of Toxicology·Sara Rodríguez-EnríquezRafael Moreno-Sánchez
Nov 28, 2014·Archives of Toxicology·Hermann M Bolt
Feb 12, 2014·The International Journal of Biochemistry & Cell Biology·Rafael Moreno-SánchezSara Rodríguez-Enríquez
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Aug 20, 2016·Biochimica Et Biophysica Acta. General Subjects·Rafael Moreno-SánchezSara Rodríguez-Enríquez
May 17, 2018·Oxidative Medicine and Cellular Longevity·Christian Silva-PlatasGerardo García-Rivas

Related Concepts

3-bromopyruvic acid
Casiopeina II-glycine
Antineoplastic Agents
Dye Exclusion Assays, Antitumor
Energy Metabolism
Glycogen
Glycolysis
Hexokinase 2
Lactates
Lymphoid Cells

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