Glioma Spheroid Cells (3D Tumor Models) Are Less Responsive to 3-Bromopyruvate than Cultured Cells: Lack of Tumors Eradication

Salah Mohamed El Sayed^{1, 2,} , Hussam Baghdadi¹, Faten M. Omran³, Ahmed M. Okashah⁴, Samer A. El-Sawy², Hytham Mahmoud¹, Wafaa A. Abdellah³, Azza Mahmoud Ahmed Abouelela³, Hassan El-Alaf⁵, Elussainy MA Elussainy⁶, Sayed Mostafa El Sayed^{7, 8}, Hesham I. Abdallah^{7, 8}, Osama Al-hadramy⁹, Tamer M. Soliman¹⁰, Amr El-Dardear¹¹, Mohamed Abdel-haleem¹² and Manal M.H. Nabo¹³

¹Department of Clinical 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 Medical Pharmacology, Sohag Faculty of Medicine, Sohag University, Egypt

⁴Academic Affairs Director And Consultant Clinical Immunologist, Al-Madinah Directorate of Health, Al-Madinah Al-Munawwarah, Ministry of Health, Saudi Arabia

⁵Department of Medical Physiology, Sohag Faculty of Medicine, Sohag University, Egypt

⁶Department of Medical Physiology, Kafr Elshekh Faculty of Medicine, Kafr Elshekh University, Egypt

⁷Anatomy and Embryology Department, Faculty of Medicine, Ain Shams University, Egypt

⁸Anatomy and Embryology Department, Faculty of Medicine, Taibah University, Saudi Arabia

⁹Division of Cardiology, Department of Medicine, Taibah Faculty of Medicine, Taibah University, Al-Madinah Al-Munawwarah, Saudi Arabia

¹⁰0Department of Clinical Pathology, Sohag Faculty of Medicine, Sohag University, Egypt

¹¹1Department of Pediatrics, Taibah Faculty of Medicine, Taibah University, Al-Madinah Al-Munawwarah, Saudi Arabia

¹²2Department of Ear, Nose and Throat, Taibah Faculty of Medicine, Taibah University, Al-Madinah Al-Munawwarah, Saudi Arabia

¹³3Department of Pediatrics, Al-Rayyan Medical Colleges, Al-Madinah Al-Munawwarah, Saudi Arabia

Cite this paper:
Salah Mohamed El Sayed, Hussam Baghdadi, Faten M. Omran, Ahmed M. Okashah, Samer A. El-Sawy, Hytham Mahmoud, Wafaa A. Abdellah, Azza Mahmoud Ahmed Abouelela, Hassan El-Alaf, Elussainy MA Elussainy, Sayed Mostafa El Sayed, Hesham I. Abdallah, Osama Al-hadramy, Tamer M. Soliman, Amr El-Dardear, Mohamed Abdel-haleem and Manal M.H. Nabo. Glioma Spheroid Cells (3D Tumor Models) Are Less Responsive to 3-Bromopyruvate than Cultured Cells: Lack of Tumors Eradication. American Journal of Cancer Prevention. 2019; 7(1):10-14. doi: 10.12691/ajcp-7-1-2

Abstract

Gliomas and glioblastomas are space-occupying brain tumors with variable aggressive behaviour. Glioblastomas are the most lethal brain tumors and are not responsive to current chemotherapy and radiotherapy. To date, no satisfactory curative treatment exists. 3-bromopyruvate (3BP) is a promising chemotherapeutic that proved effective in treating gliomas and other malignancies in so many reported studies. 3BP is both an alkylating agent and antimetabolite (pharmacological antagonist of lactate, the Warburg effect). Our previous publications proved effectiveness of 3BP in treating glioma cell lines (2D models) and early glioma spheroids (3D models) where 3BP was added early after culturing glioma cells. No report is there regarding treating well-established glioma spheroids (well-established avascular 3D tumor models) using 3BP that we report here. In this study, our data revealed that 3BP effectively and maximally killed cultured glioma cells causing cellular fragmentation that correlated with maximal glioma cell death. However, the picture was less promising when treating well-established 3D glioma spheroids with 3BP where glioma viability and size decreased significantly (in a dose-dependent manner) but not maximally. There was no significant difference in spheroids cell killing at high versus very high doses of 3BP. 3BP may face many problems regarding delivery and targeting to glioma cells inside spheroid body. A similar effect may be faced when treating clinical tumors with 3BP. 3BP formulations inside lipid nanocarriers (liposomes), PEGylated liposomes or targeted liposomes may improve 3BP-induced tumor cells killing. More future research is needed to explore the reasons why 3BP effects in cell lines were not effectively translated into 3D models and how to overcome the obstacles.

Keywords:
3-bromopyruvate spheroids glioma viability

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