Compound in Red Sage Plant May Help Control Blood Vessels that Feed Tumors

NCI CAM Annual Report-FY10

Among the most widely used plants in traditional Chinese medicine (TCM) is red sage, known in China as Danshen (Salvia miltiorrhiza). It stimulates blood flow and is used to treat inflammation, cardiovascular disease, and cerebrovascular disease. According to TCM principles, cancer is a form of tissue swelling, and thus using substances that stimulate blood flow may help treat many types of cancer.

But there is a paradox at work here, said Bin Chen, Ph.D., who was trained in TCM and pharmacology at Nanjing University of Chinese Medicine in China. “Cancers also make use of the circulatory system by growing blood vessels into a pipeline that delivers oxygen and nutri­ents to nourish and extend tumors.”

It is therefore common in the West to treat some tumors with antiangiogenic therapy, using drugs that prevent new blood vessels from growing. Dr. Chen’s research focuses on vascular-disrupting therapy, because he is not only interested in preventing new blood vessels from forming but is also seeking to destroy the existing blood vessels within the cancerous tissue.

With NCI funding*, his laboratory at the University of the Sciences in Philadelphia is conducting a pilot study of how tanshinone IIA (Tan IIA), one of Danshen’s active ingredients, might become a key piece in vascular-disrupting therapy. In previous laboratory studies on cancerous endothelial cells that line blood vessels, Tan IIA was able to attack and kill cells in several different ways. What hasn’t been studied is exactly how these effects might be marshaled to target the blood pipelines that can feed tumors throughout the body.

Dr. Chen and his colleagues will try to fill in the important details about how Tan IIA works against prostate cancer by experimenting on mice that have been implanted with human tumor cells. “We give the Tan IIA compound to the mice, and with a special imaging system we can watch to see if blood vessels grow or not,” he said. “If the impact is evident shortly after treatment begins, the Tan IIA is probably disrupting the blood vessels that are already in place.”

However, if new blood vessels do not develop in the mice, then the Tan IIA is behaving more like an antiangiogenic drug by denying the tumor the new blood supply that it needs to grow, Dr. Chen added. This effect on the tumor growth is evident only over time, because it targets the endothelial cells that are necessary for new blood vessels to grow.

“Our longstanding interest in how the vascular system affects cancer encouraged us to look at whether Tan IIA might be used to control blood flow in ways that we could exploit,” Dr. Chen explained. Because most cancer cell-killing chemotherapeutic drugs used in the West travel in the bloodstream, this work will also focus on whether Tan IIA can help deliver such drugs more effectively to the site of the tumor, Dr. Chen added.

He is also testing whether Tan IIA could be used to improve the delivery of other anticancer agents. “Tumors in the prostate and elsewhere survive in part by developing defenses against our drug therapies,” he explained. “For example, the tumors’ blood vessels are not efficient for the delivery of chemotherapy drugs circulating in the bloodstream.”

“Because Tan IIA is so safe and essentially has no side effects, we can deliver it chronically and in large amounts,” Dr. Chen said. The goal would be to change the permeability of tumor vessels to allow more of the accompanying chemotherapy drug to reach the tumors. The basic challenge with chemotherapy drugs is how toxic they can be to other parts of the body beside the tumor, he noted. If the Tan IIA allows more of the cancer drug to reach the tumor, then less of the drug overall would be needed, and thus other side effects could be reduced.