Saccharin findings boost hopes on cancer drug discovery

Research led by Griffith University’s Professor Sally-Ann Poulsen is being widely credited as anticipation builds over the potential of saccharin in the fight against cancer.

While Professor Poulsen, from Griffith’s Eskitis Institute for Drug Discovery, cautions that the research is still in its early days, there is growing excitement about the development of drugs capitalising on the anti-cancer properties of the popular sugar substitute.

The work is indeed an international effort, beginning with scientists from the University of Florence who found saccharin inhibited the actions of carbonic anhydrase IX (CA IX), a protein that helps regulate pH in and around cancer cells and allows tumours to flourish.

CA IX is found in the most aggressive and difficult to treat cancers, including in the breast, lung, liver, kidney, pancreas and brain.

Professor Poulsen’s research team then created a compound by chemically linking a molecule of glucose to saccharin, the result of which was to significantly reduce the quantity of saccharin needed to deactivate the CA IX enzyme to improve the anti-cancer properties around 1000-fold over unmodified saccharin.

Now researchers at the University of Florida have used X-ray crystallography to determine how saccharin binds to CA IX and how it or other saccharin-based compounds might be manipulated to enhance cancer treatments.

Hopes are that the development of saccharin-based drugs could slow the growth and spread of cancers, lower their resistance to chemotherapy and radiation and mitigate side-effects to healthy tissue.

“The results so far indicate the value of making more compounds from this family, identifying the strengths and liabilities and amending the work accordingly,” says Professor Poulsen.

“However, as much as there is great anticipation about where these findings may lead, we are still in the early days, taking what we have done already and striving to advance upon it.”

Papers about the research have been published in the Journal of Medicinal Chemistry and Bioorganic & Medicinal Chemistry.