Effects on Energy Metabolism of Two Guanidine Molecules, (Boc)2 -Creatine and Metformin.

Abstract

Several enzymes are involved in the energy production, becoming a possible target for new anti-cancer drugs. In this paper, we used biochemical and in silico studies to evaluate the effects of two guanidine molecules, (Boc)2 -creatine and metformin, on creatine kinase, an enzyme involved in the regulation of intracellular energy levels. Our results show that both drugs inhibit creatine kinase activity; however, (Boc)2 -creatine displays a competitive inhibition, while metformin acts with a non-competitive mechanism. Moreover, (Boc)2 -creatine is able to inhibit the activity of hexokinase with a non-competitive mechanism. Considering that creatine kinase and hexokinase are involved in energy metabolism, we evaluated the effects of (Boc)2 -creatine and metformin on the ATP/AMP ratio and on cellular proliferation in healthy fibroblasts, human breast cancer cells (MDA-MB-468), a human neuroblastoma cell line (SH-SY5Y), a human Hodgkin lymphoma cell line (KMH2). We found that healthy fibroblasts were only partially affected by (Boc)2 -creatine, while both ATP/AMP ratio and viability of the three cancer cell lines were significantly decreased. By inhibiting both creatine kinase and hexokinase, (Boc)2 -creatine appears as a promising new agent in anticancer treatment. Further research is needed to understand what types of cancer cells are most suitable to treatment by this new compound. J. Cell. Biochem. 118: 2700-2711, 2017. © 2017 Wiley Periodicals, Inc.

• Authors: Patrizia Garbati, Silvia Ravera, Sonia Scarfì, Annalisa Salis, Camillo Rosano, Alessandro Poggi, Gianluca Damonte, Enrico Millo, Maurizio Balestrino
• Journal: Journal of cellular biochemistry (J Cell Biochem) Vol. 118 Issue 9 Pg. 2700-2711 (09 2017) ISSN: 1097-4644 [Electronic] United States
• PMID: 28128472 (Publication Type: Journal Article)
• Copyright: © 2017 Wiley Periodicals, Inc.

Chemical References

• Metformin
• Hexokinase
• Creatine Kinase
• Creatine

Topics

• Cell Line, Tumor
• Creatine (chemistry, pharmacology)
• Creatine Kinase (metabolism)
• Energy Metabolism (drug effects)
• Hexokinase (metabolism)
• Humans
• Metformin (chemistry, pharmacology)
• Models, Biological