- Artificial sweeteners such as Acesulfame potassium (ACE K) might be used in the treatment of aggressive cancers by targeting carbonic anhydrase IX (CA IX) proteins.
- CA IX proteins are overexpressed in cancer tissues and can thereby contribute to the growth of malignant cells.
- Currently approved drugs can also target similar forms of carbonic anhydrase (CA) but they are not very selective and may cause several side effects.
Acesulfame potassium (ACE K), an artificial sweetener may help in the development of selective anti-cancer drugs. These drugs can selectively target carbonic anhydrase IX (CA IX), a protein associated with aggressive cancers. The findings of this study are published in the ACS' Journal of Medicinal Chemistry.
CA IX is a zinc protein that is typically found only in the gastrointestinal tract, but it is overexpressed in cancer tissues and contributes to the growth and spread of malignant cells in lung, brain and breast cancers. But the body produces 14 other forms of CA proteins that are involved in the function of normal, healthy cells.
In earlier work, Robert McKenna and colleagues reported that saccharin, the artificial sweetener in Sweet'N Low®, was more selective toward CA IX than other treatments and therefore could be a promising treatment option. But the team wanted to know if another artificial sweetener, ACE K would be an even better cancer treatment. Known as ACE K, this sweetener is marketed as Sunett® and Sweet One® and is already widely consumed in processed foods like sodas and baked goods.
They determined that ACE K is more selective than saccharin, vastly preferring CA IX over CA II. They also explored the characteristics of ACE K binding to CA IX that makes it unique compared to other inhibitors. For example, ACE K completely fills the CA IX binding site and binds directly to a catalytic zinc ion, displacing a water molecule that is still present when approved drugs bind.
This information will help researchers modify ACE K's chemical structure to create even more selective treatments that have fewer side effects.
- Akilah B. Murray , Carrie L. Lomelino, Claudiu T. Supuran, Robert McKenna. "Seriously Sweet": Acesulfame K Exhibits Selective Inhibition Using Alternative Binding Modes in Carbonic Anhydrase Isoforms, Journal of Medicinal Chemistry (2018).DOI: 10.1021/acs.jmedchem.7b01470