Chinese fir tree compound may help to combat cancer

Cancer
New research finds that a structural analog of a compound found in an endangered Chinese fir tree has cancer-fighting properties when combined with an existing cancer drug.
scientists working in lab
Scientists devised a chemical analog of a compound from a rare Chinese tree that, combined with another drug, has cancer-fighting properties.

The National Cancer Institute (NCI) estimate that doctors diagnosed well over 1,700,00 new cases of cancer in 2018, and more than 600,000 people in the United States died from the disease.

Globally, cancer continues to be one of the leading causes of death; by the year 2030, the NCI estimate that 23.6 million new cancer cases will occur.

Researchers are therefore hard at work trying to devise new strategies to fight off this chronic disease, and more and more scientists are turning to nature in search of solutions.

For instance, Medical News Today has recently reported on a study that examined the breast cancer-fighting potential of oolong tea extract; another recent study found that a synthetic analog of a compound scientists found in a Chinese tree may be able to tackle drug-resistant pancreatic cancer.

Now, Mingji Dai, an organic chemist at Purdue University in West Lafayette, IN, has lead a team of scientists who are adding to the mounting evidence that nature may hold the key to cancer therapies.

Dai collaborated with Zhong-Yin Zhang, a professor of medicinal chemistry at Purdue, to examine the molecular makeup and therapeutic potential of a tree called Abies beshanzuensis — an endangered species of a Chinese fir tree.

The researchers published their findings in the Journal of the American Chemical Society.

‘Compound 29’ effective against cancer

Dai and team created several structural analogs of the compounds found in the tree. One of them proved to be a strong inhibitor of SHP2, an enzyme that scientists have “associated with breast cancer, leukemia, lung cancer, liver cancer, gastric cancer, laryngeal cancer, oral cancer, and other cancer types.”

“[SHP2] is one of the most important anti-cancer targets in the pharmaceutical industry right now, for a wide variety of tumors,” Dai explains. “A lot of companies are trying to develop drugs that work against SHP2.”

Dai and colleagues called the compound they created “compound 30.” They explain that compound 30 binds with the SHP2 protein, forming a “covalent bond.” By contrast, most of the compounds that other researchers have developed to target SHP2 do not form such a stable bond with it.

“With others, it’s a looser binding,” Dai says. “Ours forms a covalent bond, which is more secure and long-lasting.”

“But we also wondered whether this type of molecule could interact with other proteins,” the researcher continues.

So, to find out, the team used a so-called compound 29 — an analog that is only slightly different structurally from compound 30 — and attached a chemical tag to it in order to use it as “bait” and “catch” other proteins.

Doing so resulted in singling out another enzyme POLE3, which aids DNA synthesis and repair. So, POLE3 and compound 29 interacted, but compound 29 on its own did not affect cancer cells.

This scenario suggested to the researchers that combining compound 29 with a cancer drug that targets DNA synthesis might be effective. Dai and team screened for such drugs and found that etoposide was a good candidate.

Compound 29 alone doesn’t kill cancer, but when you combine it with etoposide, the drug is much more effective […] This could improve some of the cancer drugs used today, and it also tells us something new about the function of POLE3.”

Mingji Dai

“People weren’t targeting this protein for cancer treatment before, but our findings offer a new strategy for killing cancer cells,” concludes the researcher.

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