Saccharin as Cancer Fighter: McKenna "New" Gold
Background:
Carbonic anhydrases (CAs) are a large family of zinc
metalloenzymes that catalyze the reversible hydration of carbon dioxide. They
participate in a variety of biological processes, including respiration,
calcification, acid-base balance, bone resorption, etc. CA IX (CA 9) is a
transmembrane protein and is one of only two tumor-associated carbonic anhydrase
isoenzymes known. It is expressed in all clear-cell renal cell carcinoma, but
is not detected in normal kidney or most other normal tissues. It may be
involved in cell proliferation and transformation.
Saccharin (E954) is an artificial sweetener with effectively
no food energy which is about 400 times as sweet as sucrose or table sugar. It
is used to sweeten products such as drinks, candies, cookies, medicines, and
toothpaste. It is now the third-most
popular artificial sweetener behind sucralose and aspartame. Considering that sugar is prepared from
organic plants such as corn, sugarcane etc and saccharin was prepared from
product obtained from coal tar, saccharin always carried a stigma with it. This
stigma was further aggravated in 1970s, when scientists conducting a study
discovered a link between saccharin and bladder cancer in rats. The USFDA got
the chance they wanted and they made it mandatory for the manufacturer to put a
warning in all packaging.
In late 1990s, the National Toxicology Program and the International
Agency for Research on Cancer took a closer look at all available information
concerning saccharin and determined it did not cause cancer in humans. Later
on, in 2010, Environmental Protection Agency (EPA) removed saccharin from its
list of hazardous substances.
At Present:
Now, in a shocking turn of events, a new study indicates
that the artificial sweetener can actually be helpful in fighting cancer.
Saccharin's potential use in the development of new
anticancer drugs is due to the way in which it binds to and deactivates carbonic
anhydrase IX. It does not affect the
other similar proteins that are required to keep the body healthy.
Using X-ray
crystallography researchers have concluded how saccharin binds to carbonic
anhydrase IX. The researchers have also investigated the ways in which
saccharin or saccharin-based compounds might be altered to improve their
binding capabilities and anticancer potential. Another independent team took this work further by creating a compound in which a
glucose molecule is chemically linked to saccharin. The compound reduced the
amount of saccharin needed to inhibit carbonic anhydrase IX and was 1,000 times
more likely to bind to the protein than saccharin alone.
Presently, the team are testing how saccharin and
saccharin-based compounds affect breast and liver cancer cells. If these
preliminary tests prove to be successful, the team could look to commence
animal studies.
The findings of McKenna (University of Florida) and his colleagues were presented at the 249th National Meeting & Exposition of the American
Chemical Society (ACS).
