University Research Looks at Antioxidants’ Potential Role in Cancer Therapy

Microscope Image of cells
Leukaemia cells and a macrophage. Macrophages are normal 'healthy' white blood cells, part of the immune system. The University team’s research has shown that BCAT1 prevents the leukaemia cells from developing into macrophages. This block in development is what defines Acute Myeloid Leukaemia.

Scientists have been looking at a particular protein (enzyme) and discovered that it plays a role in regulating free radicals in acute myeloid leukaemia cells. This could lead to better therapeutic treatment of blood cancer.

“This discovery challenges the way we think about how enzymes function in cancer and forces us to think about things in a different way,” said Dr Steven Coles. “This protein was once thought to be doing something very specific. It’s doing something unexpected, it has another role.”

The enzyme in question is known as BCAT1. Part of the BCAT1 structure, called a CXXC motif, was discovered by Worcester scientists to have an antioxidant role in acute myeloid leukaemia cells. When they analysed the function of the CXXC motif, they found that it reduced the levels of free radicals (highly reactive molecules produced inside cells, that cause cellular damage). The findings have now been published in the journal Antioxidants.

Lead author Dr James Hillier, who recently graduated with his PhD from the University, focussed on this research for his doctoral studies under the guidance of Senior Lecturers in Biochemistry, Dr Coles and Dr Amy Cherry, who are part of the University’s Worcester Biomedical Research Group. Other Worcester students worked on the project too, including; final year Biochemistry undergraduate Gemma Allcott, as part of her dissertation, and Laura Guest for her Masters’ in Human Biology.

Dr Cherry said that if free radical levels get too high in a human body cell it dies. “In health terms this can be a negative, but, in fighting cancer, those cells need to be killed,” she explained. “Cancer is essentially cells dividing and growing in an out-of-control manner. The BCAT1 enzyme was found by our scientists to protect cancer cells against high levels of free radicals - which would otherwise kill them - by neutralising them.

“We know that free radical production is important in the generation of cancer. This enzyme’s got this important role in terms of managing oxidant levels in cancer cells, which keeps cancer cells dividing. In protecting these cells against free radicals, we know this enzyme is actually helping cancer cell survival.”

Dr Coles said: “We have known about this enzyme for over 50 years and it’s got a ‘normal’ metabolic role inside the cell - that was all we thought it did. We didn’t know it was doing this and, if BCAT1 can protect cancer cells from free radicals, what other enzymes existing in cancer also do it? We’re the first to show that BCAT1 has this antioxidant role in this context. Therefore, removing it or blocking it could have a therapeutic effect.”

The paper, titled BCAT1 CXXC Motif Provides Protection Against ROS in Acute Myeloid Leukaemia Cells, can be viewed in the journal Antioxidants.