Cancer is one of the leading causes of mortality worldwide. In the United States alone, more than 600,000 patients have died from the disease. In 2018, more than 1.7 million Americans were diagnosed with various forms of cancer. The National Cancer Institute predicts that the total number would increase to a staggering 23.6 million by 2030.
Researchers are searching for safer and more effective solutions for cancer. Many of them are investigating natural sources of potential anti-cancer compounds. In a separate study conducted by the Saint Louis University in 2018, researchers tested the ability of oolong tea extract to fight cancer. That same year, another team, this time from the Roswell Park Comprehensive Cancer Center, reported that a synthetic analog of camptothecin might work on drug-resistant forms of pancreatic cancer. (Related: Natural compound from the Pacific yew tree may be the next big thing in cancer treatments.)
A natural compound in a rare Chinese fir has cancer-fighting potential
For their study, Purdue researchers Mingji Dai and Zhong-Yin Zhang examined the molecular composition and cancer-fighting potential of Baishan fir (Abies benshanzuensis). The fir totters on the brink of extinction — only three individuals remain in the world, and all three occupy the same grove in a Chinese nature preserve.
The researchers made several chemicals that bore similar structures to the tree's natural compounds. One of the analogs suppressed the activity of the SHP2 enzyme. Earlier studies established a link between SHP2 and numerous types of cancer. The protein contributed to the onset of breast cancer, gastric cancer, leukemia, liver cancer, and lung cancer.
“[SHP2] is one of the most important anti-cancer targets in the pharmaceutical industry right now, for a wide variety of tumors,” remarked Dai. “A lot of companies are trying to develop drugs that work against SHP2.”
He and his colleagues gave the name “compound 30” to the promising anti-cancer substance. The chemical formed a covalent bond with the SHP2 protein. A covalent bond is a strong chemical interaction between different atoms that remains stable for long periods. Of the structural analogs developed by the Purdue team, only compound 30 achieved such a tightly-knit bond with SHP2.
By conserving endangered plant species, humans might find cures for cancer
Dai and his colleagues pondered the possibility of compound 30 interacting with proteins other than SHP2. They tested “compound 29,” an analog with a very similar structure to the other chemical. In their experiment, the Purdue researchers marked compound 29 with a chemical tag. They evaluated any proteins that interacted with the chemical.
They found that compound 30 bound itself to an enzyme called POLE3. The protein helped produce DNA and repaired any damage incurred by genetic material. They concluded that compound 29 did not exert any effect on cancer by itself. However, the chemical increased the activity of a protein that fought cancer by repairing damaged DNA.
Further experimentation showed that compound 29 achieved a similar supportive effect with the anti-cancer drug etoposide. By boosting the effectiveness of etoposide, the compound reduced the dosage of the drug required.
“Compound 29 alone doesn't kill cancer, but when you combine it with etoposide, the drug is much more effective,” explained Dai. “This could improve some of the cancer drugs used today, and it also tells us something new about the function of POLE3.”
Hopefully, the interest in compounds 29 and 30 as potential anti-cancer treatments also contributes to the preservation of the Baishan fir.
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