Enhancing anticancer effects, decreasing risks and solving practical problems facing 3-bromopyruvate in clinical oncology: 10 years of research experience

Abstract

3-Bromopyruvate (3BP) is a promising powerful general anticancer agent. Unfortunately, 3BP release faces many practical and biochemical problems in clinical human oncology, for example, 3BP induces burning venous sensation (during intravenous infusion) and rapid inactivation by thiol groups of glutathione and proteins. 3BP exhibits resistance in glutathione-rich tumors without being able to exert selective targeting. 3BP does not cross the blood–brain barrier and cannot treat nervous system tumors. Importantly, 3BP cannot persist in tumor tissues due to the phenomenon of enhanced permeability and retention effect. Here, the author presents the practical solutions for clinical problems facing 3BP use in clinical oncology, based on over 10 years of experience in 3BP research. Crude (unformulated 3BP that is purchased from chemical companies without being formulated in liposomes or other nanocarriers) should not be administered in clinical oncology. Instead, 3BP is better formulated with liposomes, polyethylene glycol (PEG), PEGylated liposomes (stealth liposomes) or perillyl alcohol that are used currently with many chemotherapeutics for treating clinical tumors in cancer patients. Formulating 3BP with targeted liposomes, for example, with folate, transferrin or other ligands, improves tumor targeting. Formulating 3BP with liposomes, PEG, stealth liposomes or perillyl alcohol may improve its pharmacokinetics, hide it from thiols in the circulation, protect it from serum proteins and enzymes, prevent burning sensation, prolong 3BP’s longevity and facilitate crossing the BBB. Formulating 3BP with stealth liposomes protects 3BP from the reticuloendothelial cells. Liposomal 3BP formulations may retain 3BP better inside the relatively large tumor capillary pores (abolish enhanced permeability and retention effect) sparing normal tissues, facilitate new delivery routes for 3BP (eg, topical and intranasal 3BP administration using perillyl alcohol) and improve cancer cytotoxicity. Formulating 3BP may be promising in overcoming many obstacles in clinical oncology.

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Keywords:

• 3-bromopyruvate
• 3BP release
• PEG formulation
• practical problems
• liposomes and targeting cancer

Acknowledgments

The author is grateful to professor Kiyoshi Fukui (the prominent well-known scientist in D-amino acid oxidase research), Division of Enzyme Pathophysiology, The Institute for Enzyme Research, The University of Tokushima, Japan. Professor Kiyoshi Fukui was kind and patient in teaching the author how to write a scientific paper and how to do scientific research in his highly prestigious laboratory with the help of his excellent and co-operative Japanese and international staff members. Under kind patronage and support by Professor Kiyoshi Fukui, three papers in 3-bromopyruvate research were published. The author expresses that he can never reward the favor of professor Kiyoshi Fukui for his patience, support and endless help. The author is grateful to The University of Tokushima, the Japanese people and Japan for the scientific make-up that enabled him to write this article. The author is also grateful to Dr Stephen Strum (the highly knowledgeable board certified American oncologist), Dr Orn Adalsteinsson and Dr Jagadish for their fruitful scientific discussions that benefited a lot in 3BP research. The author is also so grateful to Taibah University, Saudi Arabia for allowing a helpful environment to conduct this study. The author is very grateful to Obaidi, Mr Raed Ali Al-Raddadi, Mr Sultan Al-Hussini, Mr Mohamed Abdelsamad and Mr Wael Barakat from the administrative department, College of Medicine, Taibah University for their technical help and support to this work.

The author declares that there is no financial or non-financial competing interests with any other partner. There is no financial benefit. The article is fully supported by the author.

Disclosure

The author reports no conflicts of interest in this work.