Natural Product Shows Effectiveness in Combating Colorectal Cancer

By Julianne Heberlein, Werner H. Kirsten Student Intern, Contributing Writer; visuals courtesy of Nancy Colburn and Matthew Young, Basic Research Laboratory, NCI Center for Cancer Research
Scientific Researchers

From left to right: Weidong Li, principal investigator, China Academy of Chinese Medical Sciences in Beijing; Nancy Colburn, Ph.D., scientist emeritus, Basic Research Laboratory, NCI Center for Cancer Research (CCR); and Matthew Young, Ph.D., formerly of the Basic Research Laboratory, NCI CCR.

An herbal extract used for centuries to prevent heart disease has now been shown to be effective against colorectal cancer when tested in laboratory cell cultures.

Scientists from NCI at Frederick found that the natural extract cryptotanshinone (CPT) stops the uncontrolled cell growth characteristic of cancer by interfering with a protein that has been implicated in several cancers, including those of the colon and rectum. The results appear in the journal Molecular and Cellular Biochemistry.

Colorectal cancer is the third most common cancer in men and women in the United States and the fourth most fatal malignancy. Early screening can prevent the disease by allowing for the complete surgical removal of precancerous growths. However, colorectal cancer is often diagnosed during the late stages, which makes treatment more difficult and less tolerable.

CPT has a long history as an herbal remedy. The compound is isolated from the root of an Asian medicinal plant called Salvia miotiorrhiza, also known as “Danshen.” The plant is native to China and Japan, and is located in grassy areas such as forests and hillsides. In Chinese medicine, CPT has been clinically used to treat a variety of diseases, including cardiac fibrosis, blood clotting in heart disease, acute lung injury, and arthritis.

Previously, the natural compound had been shown to inhibit growth in various cancers, including prostate, leukemic, melanoma, and glioma. Because of its previous success, the research group decided to explore its effect on colorectal cancer. The team included Nancy Colburn, Ph.D., now scientist emeritus, Basic Research Laboratory, NCI Center for Cancer Research (CCR), and Matthew Young, Ph.D., formerly of the Basic Research Laboratory, NCI CCR, in collaboration with Weidong Li, Ph.D., principal investigator at Guang’anmen Hospital, China Academy of Chinese Medical Sciences in Beijing, and Shakir Saud of the NCI Division of Cancer Prevention.

Using colonies of colon cancer cells maintained for research purposes, the researchers added CPT in various doses over a period of several days and analyzed the effect.

They found that CPT directly interfered with cancer cell growth and blocked a DNA-binding protein known as Stat3 that regulates growth, survival, and variation within cells. When overactive, Stat3 can turn cells cancerous and drive tumor progression. At similar doses, CPT did not harm noncancerous cells.

Currently, chemotherapy is the primary treatment for colorectal cancer; however, its harsh side effects greatly degrade a patient’s quality of life. CPT’s limited side effects make it an attractive option for use in combination with other conventional cancer therapies.

“These findings indicate that CPT may be a potential candidate for the treatment and prevention of colorectal cancer, in part by inhibiting the activation of Stat3,” the scientists wrote.

More than half of the drugs approved by the U.S. Food and Drug Administration for use as cancer treatments are natural products or derived from natural products.  In laboratories around the country, cancer researchers are also exploring ways to use natural products that show anticancer effects when combined with standard chemotherapy treatments. The goal is to increase potency while reducing side effects.

The chemical structure of cryptotanshinone, isolated from an herbal extract, has been shown to interfere with cancer cell growth in colon cancer cells. The red atoms indicate oxygen.Danshen (Salvia miltiorrhiza), the Asian medicinal plant from which cryptotanshinone is isolated.