Artificial sweeteners can help treat aggressive cancers

Artificial sweeteners are used in diet drinks and foods, but one day they can also be used to treat carbonic anhydrase IX (CA IX), a protein associated with aggressive cancer. Although several drugs have been approved for similar forms of CA, they are not selective and may cause side effects, including vomiting and fatigue. Now, researchers report in the ACS Journal of Medicinal Chemistry that artificial sweeteners may lead to the development of more selective treatments.

CA IX is a ZINC protein that is usually found only in the gastrointestinal tract, but is overexpressed in cancer tissues and causes the growth and spread of malignant cells in lung cancer, brain cancer, and breast cancer. But the body produces 14 other forms of CA protein, which are involved in the function of normal, healthy cells. In earlier work, Robert McKenna and colleagues reported that the sweetener saccharin in Sweet’NLow® has a higher selectivity for CA IX than other treatments, so it may be a promising treatment. But the team wanted to know whether another artificial sweetener, acesulfame potassium, would be a better treatment for cancer. This sweetener is called ACE K and is sold as S.

The CA IX protein is difficult to purify, so the researchers created a genetically engineered version called "CA IX mimetics." Then, they studied the interaction of ACE K and other Inhibitors with CA IX mimetics, and a form called CA II found throughout the body. They determined that ACE K is more selective than saccharin, and highly preferred CA IX rather than CA II. They also explored the characteristics of the combination of ACE K and CA IX, making them unique compared to other inhibitors. For example, ACE K completely fills the CA IX binding site and directly binds to catalytic zinc ions, replacing Water molecules that are still present when the approved drug binds. This information will help researchers modify the chemical structure of ACE K to create more selective treatments and reduce side effects.