Surprise Anticancer Properties of Laboratory Molecule Discovered

Surprise Anticancer Properties of Laboratory Molecule Discovered
Surprise Anticancer Properties of Laboratory Molecule Discovered - Nobel laureate Dr. Aziz Sancar at an event in 2016. (Photo by Jon Gardiner/UNC-Chapel Hill)

Nobel laureate Dr. In the research of Aziz Sancar's group at UNC School of Medicine, interesting results emerged. He states that a common molecular tool for DNA labeling has anticancer properties that deserve further study, particularly for brain malignancies. Researchers at the UNC School of Medicine have found that a molecule called EdU, which is often used to label DNA in laboratory experiments, is actually considered DNA damage by human cells.

After all, he was surprisingly initiating an out-of-control DNA repair process. This was an important discovery. The aim of the study is to trigger DNA repair of affected cells, including cancer cells.

Given its toxicity and preference for rapidly dividing cells, the finding, reported in the Proceedings of the National Academy of Sciences, raises the possibility of EdU being used as the basis of a cancer treatment.

D., who is also a member of the UNC Lineberger Comprehensive Cancer Center and Sarah Graham Kenan, Professor of Biochemistry and Biophysics at the UNC School of Medicine. According to Aziz Sancar, “Edu's unexpected features make it worth it. More research is needed on its potential, particularly against brain cancers. We would like to emphasize that this is a fundamental but important scientific discovery. “The scientific community has a long way to go to determine whether EdU can really be used as a weapon against cancer.”

The popular scientific tool EdU (5-ethynyl-2′-deoxyuridine) was first created in 2008 as a chemical analogue of adenine (A), the DNA building block thymidine, which stands for the letter "T" in the DNA code of cytosine. (C), guanine (G), and thymine (T). In lab tests, scientists add EdU to cells instead of thymidine in DNA.

Unlike other thymidine analogs, it has a useful chemical "handle" to which fluorescent probe molecules will bind tightly. Therefore, it can be used to identify and track DNA quite quickly and effectively, for example in studies of the DNA replication process during cell division.

This method of using EdU as a tool by scientists has been documented in thousands of studies since 2008. Aziz Sancar is the recipient of the 2015 Nobel Prize in Chemistry for his important work on DNA repair. When his group began using EdU, it was surprising to discover that EdU-tagged DNA induced a DNA repair response even when not exposed to DNA-damaging agents such as ultraviolet radiation.

“This was a huge shock,” Sancar said. "That's why we decided to investigate further."

After the strange observation, the team found that EdU altered the DNA in a way that caused a repair reaction known as nucleotide excision repair, for reasons still unknown. In this procedure, a small portion of damaged DNA is removed and a new DNA sequence is synthesized in its place. This system is responsible for repairing much of the DNA damage caused by UV radiation, cigarette smoke, and chemotherapy drugs. Because each new repair chain contains EdU and thus triggers a new repair reaction, the researchers used high-resolution mapping to identify locations of EdU-induced excision repair across the genome.

Although the exact mechanism of EdU's harmful effects on cells is not known, this fact has been accepted. The research team's findings strongly imply that EdU kills cells by causing a failed excision repair process that causes the cell to kill itself through a process known as apoptosis, a type of programmed cell death.

According to Sancar, this finding was intriguing in itself because it showed that those who label DNA with EdU should consider the fact that doing so can promote rapid excision repair.

According to Sancar, thousands, if not millions, of researchers are currently using EdU to study DNA replication and cell proliferation in laboratory experiments, unaware that human cells recognize this as DNA damage.

Sancar and colleagues also observed that EdU is incorporated into DNA only in actively dividing cells, while most healthy cells in the brain do not divide, suggesting that EdU's properties may form the basis for a successful brain cancer drug. Therefore, in theory, EdU could kill rapidly proliferating malignant brain cells while preserving the constantly proliferating healthy brain cells.

Sancar and his group plan to continue their previous partnerships with other academics to explore the potential anticancer effects of EdU.

Interestingly, however, no one followed these findings, according to Sancar. “Previous research has already discovered evidence that EdU kills cancer cells, specifically brain cancer cells,” he said.

Source: The University of South Carolina

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