eng Science and Education Publishing Journal of Cancer Research and Treatment 2374-2003 2018-03-21 6 1 18 24 10.12691/jcrt-6-1-4 JCRT2018614 article Salah Mohamed El Sayed salah_medicine@yahoo.com, salahfazara@yahoo.com 1 2 Hussam H. Baghdadi 2 Nassar Ayoub Abdellatif Omar 3 4 Amal Nor Edeen Ahmad Allithy 5 6 Nahed Mohammed Hablas 7 Ahmed Ragab Fakhreldin 8 Reham Abelsalam Mariah 8 9 Momen El-Shazley 10 11 Mongi Ayat 11 Sayed Mostafa 12 Mostafa Abu-el Naga 13 14 Mohamed Abdel-Halim 15 Department of Biochemistry and Molecular Medicine, Taibah Faculty of Medicine, Taibah University, Al-Madinah Al-Munawwarah, Saudi Arabia Department of Anatomy, Sohag Faculty of Medicine, Sohag University, Egypt Department of Pathology, Sohag Faculty of Medicine, Sohag University, Egypt Department of Pediatrics, Tanta University Faculty of Medicine, Tanta, Gharbia, Egypt Department of Pediatrics, Aswan Faculty of Medicine, Aswan University, Egypt 0Department of Medicine, Taibah Faculty of Medicine, Taibah University, Al-Madinah Al-Munawwarah, Saudi Arabia 2Division of cell biology, Ain Shams Faculty of Medicine, Egypt 3Department of anatomy and Embryology, Faculty of Medicine, Rabigh branch, King Abdul-Aziz University, Saudi Arabia 5Department of Ear, Nose and Throat, Taibah Faculty of Medicine, Taibah University, Al-Madinah Al-Munawwarah, Saudi Arabia 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. http://pubs.sciepub.com/jcrt/6/1/4/jcrt-6-1-4.pdf citrate phosphofructokinase Glioblastoma apoptosis