Could an Artificial Sweetener Be Used To Fight Cancer?

MedicalResearch.com Interview with:

Prof. Robert McKenna PhD Department of Biochemistry and Molecular Biology College of Medicine, University of Florida Gainesville, Florida 32610

Prof. McKenna

Prof. Robert McKenna PhD
Department of Biochemistry and Molecular Biology
College of Medicine, University of Florida
Gainesville, Florida 32610

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Carbonic anhydrase IX (CA IX) is an enzyme that is typically only found in the GI tract, but is overexpressed in cancerous tissue. This enzyme functions to regulate the pH of tumor cells, so we hypothesize that disruption of this role will lead to tumor cell death.

This study analyzes the inhibition of CA IX using an artificial sweetener, acesulfame potassium (AceK). Our research provides a structural perspective to understand the selectivity of aceK for CA IX over an off-target enzyme, CA II. We discovered that aceK binds directly to an active site zinc in CA IX whereas the sweetener anchors through a zinc-bound water in CA II.

MedicalResearch.com: What should readers take away from your report?

Response: While this study is not meant to suggest artificial sweeteners as a cancer therapy, our report raises awareness for CA IX as a biomarker in multiple cancer types and discusses the possibilities of using carbohydrates in the design of new CA IX inhibitors. 

MedicalResearch.com: What recommendations do you have for future research as a result of this work?

Response: In conjunction with previous studies analyzing the binding of saccharin and sucrose to CA IX, this finding further supports the use of carbohydrates to act as lead compounds in the design of CA IX selective inhibitors. The use of aceK as a building block to design larger inhibitors can increase the number of interactions between the compound and active site, improving selectivity.  

Citations:

J Med Chem. 2018 Jan 5. doi: 10.1021/acs.jmedchem.7b01470. [Epub ahead of print]

“Seriously Sweet”: Acesulfame K Exhibits Selective Inhibition Using Alternative Binding Modes in Carbonic Anhydrase Isoforms.

Murray AB1, Lomelino CL1, Supuran CT2, McKenna R1.

 

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