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Pharmacological Double Inhibition of Glycolysis in glioblastoma Multiforme Cells Maximizes Cancer Cell Killing: A Synergism between Citrate and 3-bromopyruvate
Faten M. Omran, Hussam Baghdadi, Tamer M. Soliman, Osama Alhadramy, Momen El-shazley, Samer A. El-Sawy, Hytham Mahmoud Abdel-Latif, Wafaa A. Abdellah, Azza Mahmoud Ahmed Abouelella, Amr El-Dardear, Mohamed Abdel-haleem, Elhussainy MA Elhussainy, Hassan El-Alaf, Nassar Ayoub, Sayed Mostafa El Sayed, Hesham I. Abdallah, Salah Mohamed El Sayed, Mongi Ayat, Ahmed Mohamed Shehata
American Journal of Pharmacological Sciences
.
2020
, 8(1), 1-6 doi:10.12691/ajps-8-1-1
Figure 1.
Citric acid is a natural organic acid. A. Molecular structure of citric acid. B. Citric acid in enormously present in citrus fruits
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Figure 2.
Glycolysis is the basic and essential primary source of energy in body cells. It is a ten-step metabolic pathway. Glycolysis is more vital for cancer cells than for normal cells.
A.
3-bromopyruvate inhibits hexokinase enzyme while citrate inhibits phosphofructokinase. Simultaneous inhibition of both creates glycolysis double inhibition.
B.
Warburg effect occurs in cancer cells due to permanent conversion of pyruvate into lactate through activity of lactate dehydrogenase
Full size figure and legend
Figure 3.
Glycolysis inhibitors decrease cancer cells viability.
A. Pyruvate, 3-bromopyruvate and lactate are structural analogs. Lactate-based benefits to cancer cells include enhancing angiogenesis, metastasis, invasion, proliferation, migration, chemoresistance, radioresistance and acidic tumor microenvironment. B. Effects of serial citrate concentrations on viability of human glioblastoma cells (U373MG)
Full size figure and legend
Figure
4
. Citrate exerts a synergistic effect with 3-bromopyruvate (A) Glycolysis double inhibition through combining serial doses of citrate with 3-bromopyruvate in C6 glioma cells. (B) Effect of glycolysis double inhibition on U373MG human GBM cells. (C) Effect of glycolysis double inhibition on morphology of U373MG. Data are (Mean ± SEM) of the percentages of the control values of three independent experiments. *p<0.05, ** p<0.01 and ***p<0.001 indicate significance between control and different treatment conditions and also between treatment conditions within the same group
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