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Marín-Hernández A1, Rodríguez-Enríquez S, Vital-González PA, Flores-Rodríguez FL, Macías-Silva M, Sosa-Garrocho M, Moreno-Sánchez R. Determining and understanding the control of glycolysis in fast-growth tumor cells. Flux control by an over-expressed but strongly product-inhibited hexokinase. FEBS J. 2006 May; 273(9): 1975-88.

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The Antioxidant Glycolysis Inhibitor (Citric Acid) Induces a Dose-dependent Caspase-mediated Apoptosis and Necrosis in Glioma Cells

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

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

3Department of Anatomy, Sohag Faculty of Medicine, Sohag University, Egypt

4Department of Anatomy, Al-Rayyan Medical College, Al-Madinah Al-Munawwarah, Saudi Arabia

5Department of Pathology, Sohag Faculty of Medicine, Sohag University, Egypt

6Department of Pathology, Al-Ghad Faculty of Health Sciences, Al-Madinah Al-Munawwarah, Saudi Arabia

7Department of Pediatrics, Tanta University Faculty of Medicine, Tanta, Gharbia, Egypt

8Department of Pediatrics, Aswan Faculty of Medicine, Aswan University, Egypt

9Department of Medical Biochemistry, Tanta Faculty of Medicine, Tanta University, Cairo, Egypt

100Department of Medicine, Taibah Faculty of Medicine, Taibah University, Al-Madinah Al-Munawwarah, Saudi Arabia

111Department of Family and Community Medicine, Faculty of Medicine, Sohag University, Egypt

122Division of cell biology, Ain Shams Faculty of Medicine, Egypt

133Department of anatomy and Embryology, Faculty of Medicine, Rabigh branch, King Abdul-Aziz University, Saudi Arabia

144Department of anatomy and Embryology, Faculty of Medicine, New Damietta, Al-Azhar University, Egypt

155Department of Ear, Nose and Throat, Taibah Faculty of Medicine, Taibah University, Al-Madinah Al-Munawwarah, Saudi Arabia


Journal of Cancer Research and Treatment. 2018, Vol. 6 No. 1, 18-24
DOI: 10.12691/jcrt-6-1-4
Copyright © 2018 Science and Education Publishing

Cite this paper:
Salah Mohamed El Sayed, Hussam H. Baghdadi, Nassar Ayoub Abdellatif Omar, Amal Nor Edeen Ahmad Allithy, Nahed Mohammed Hablas, Ahmed Ragab Fakhreldin, Reham Abelsalam Mariah, Momen El-Shazley, Mongi Ayat, Sayed Mostafa, Mostafa Abu-el Naga, Mohamed Abdel-Halim. The Antioxidant Glycolysis Inhibitor (Citric Acid) Induces a Dose-dependent Caspase-mediated Apoptosis and Necrosis in Glioma Cells. Journal of Cancer Research and Treatment. 2018; 6(1):18-24. doi: 10.12691/jcrt-6-1-4.

Correspondence to: Salah  Mohamed El Sayed, Department of Biochemistry and Molecular Medicine, Taibah Faculty of Medicine, Taibah University, Al-Madinah Al-Munawwarah, Saudi Arabia. Email: salah_medicine@yahoo.com, salahfazara@yahoo.com

Abstract

Background: Glioma tumors are still a big challenge being incurable with current chemotherapy and radiotherapy treatments. Surgical treatment of glioma needs adjuvant effective targeting therapy for better glioma cell treatment. Citrate is a well-known antioxidant organic acid abundant in citrus fruits and is an inhibitor of glycolysis through targeting the glycolytic enzyme phosphofructokinase, one of the key enzymes of glycolysis. Citrate is a natural product that is formed inside mitochondria during Krebs cycle to the extent that Krebs cycle is often referred to as citric acid cycle. It was reported that glioma cells are driven by glycolysis where glioma cells upregulates the expression of glycolysis genes and enzymes. Objectives: This aim is to investigate effect of citrate on glioma cells viability, morphology and moge of glioma-induced cell death. Methodology: In this study, citrate-induced glioma cell death was investigated using MTT assay, western blot analysis and flowcytometric evaluation was done to C6 glioma cells. Results: Citrate induced a potent anti-glioma effect by significantly decreasing viability of C6 glioma cells in a dose-dependent manner. Flow cytometric analysis revealed that at 5 mM, citrate induced a caspase-dependent apoptotic glioma cell death. Higher doses of citrate (9 mM) induced necro-apoptotic glioma cell death. Conclusion: citrate may be a promising therapeutic treatment for glioma and glioblastoma. Citrate-rich fruits are strongly recommended as a nutritional treatment for glioma patients.

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