Artificial or low-calorie sweeteners might help us in treating in aggressive cancer, finds a new study.
Highlights
- 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.
The CA IX protein is difficult to purify, so the researchers created a genetically engineered version, called "CA IX mimic." They then studied the interactions of ACE K and other inhibitors with CA IX mimic and with a form found throughout the body called CA II.
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.
Reference
- 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