Enzyme May Be Key to Unlocking Treatment for Cancer, Diabetes, College of Pharmacy Researcher Says

"the ultimate goal is to generate small-molecule therapeutics targeting glyoxalase II for the treatment of diseases such as cancer and diabetes.”

Preliminary studies conducted by James Galligan, PhD, an assistant professor at the University of Arizona College of Pharmacy, suggest the enzyme glyoxalase II (GLO2) is a strong candidate for drug developers to consider as a potential treatment for breast cancer and diabetes.

The enzyme plays a key role in the rate of cell growth and a therapy targeting this function may help to control the development and spread of certain diseases. Dr. Galligan, who specializes in cellular metabolism and how diseases originate, recently received a five-year $1.8 million research grant from the National Institutes of Health (NIH) to continue his investigation into this possibility.

The glyoxalase system is a set of biological compounds that accelerate chemical reactions in the body and help protect against cellular damage. The system is made up of two enzymes, glyoxalase I and glyoxalase II, both of which are found in a variety of species, including single-celled organisms, plants and mammals, suggesting the functions performed by the glyoxalase system are fundamental to biological life.

In their preliminary study, which appeared in the journal Cell Chemical Biology, Dr. Galligan’s research team demonstrated that when the function of GLO2 is inhibited, glycolysis – the process by which cells use glucose for energy – is slowed down. This results in a slower rate of cell growth, which makes GLO2 an appealing target for treatment of diseases, most notably cancer, which results from unchecked cell growth.

Cellular metabolism affects every facet of life on Earth. The process involves a complex sequence of biochemical reactions that occur in living organisms to maintain life. The disruption of this activity is the root cause of numerous diseases including many forms of cancer and diabetes.

For instance, glyoxalase is thought to play a crucial role in insulin-dependent diabetes mellitus, with expression of both forms (GLO1 and GLO2) elevated in patients who suffer from the disease. A glyoxalase connection also is suspected in breast cancer and certain urological malignancies such as prostate cancer. Related papers, with Dr. Galligan as co-author, appear in the journals ACS Chemical Biology and PNAS.

In collaboration with researchers at the University of Colorado Anschutz Medical Campus, Dr. Galligan has identified a unique protein modification that regulates the breakdown of glucose as well as cell growth by using the GLO2 enzyme. Funded through the National Institute of General Medical Studies (NIGMS), an NIH unit, this new grant will support a research study, seeking to expand our understanding of the role of glyoxalase II in protein modification and its impact in maintaining health and causing disease.

“We aim to understand how glyoxalase II regulates cell growth and energy production in cells in the short-term,” Dr. Galligan explained. “Although the ultimate goal is to generate small-molecule therapeutics targeting glyoxalase II for the treatment of diseases such as cancer and diabetes.”

Research reported in this publication was supported by the National Institute of General Medical Sciences, a unit of the National Institutes of Health, under Award No. R35GM137910.

This story was originally published by University of Arizona Health Sciences