Studying Cork Tree Extract and Exercise as Treatments for Prostate Cancer
Mays Cancer Center Annual Report
Legend holds that Shennong, the father of traditional Chinese medicine, had a transparent body which made it all the easier to observe the effects of medicinal herbs on his system. Amurense, an extract from the bark of the Amur cork tree native to China, made his list of the 50 noble herbs as an anti-inflammatory. Thousands of years later, UT Health San Antonio researchers are taking another look at amurense. Its potential as a powerful therapeutic in treating prostate cancer is getting clearer and clearer.
Prostate cancer will be diagnosed in one in eight men during his lifetime, according to the American Cancer Society, and is the second leading cause of cancer death in men. Current treatments often come with undesirable side effects and therapeutics to slow or stop progression while easing symptoms are desperately needed. Darpan Patel, PhD, associate professor of research in the School of Nursing, believes cork tree bark may do just that.
Research on amurense in mouse models was funded by a grant from the Population Science and Prevention pilot program at the Mays Cancer Center. Dr. Patel, along with lead investigator A. Pratap Kumar, PhD, co-leader of the Prevention and Population Science Program at the cancer center and CTRC 40th Anniversary Endowed Distinguished Professor in Oncology, studied amurense in mouse models for 20 weeks.
Research showed that pure Amur cork tree extract, marketed as the natural supplement Nexrutine®, is just as effective as exercise in preventing the progression of aggressive prostate cancer by reducing tumor growth by 62 percent.
“This amurense compound is capable of modifying the pro-inflammatory cytokines that are associated with the progression of tumors by affecting multiple signaling pathways,” Dr. Patel says. There is also early evidence it can impact angiogenesis. This finding is significant because tumors thrive in a low-oxygen environment by forming abnormal microcirculatory systems. “It’s the same theory we have that explains the proven effectiveness of exercise,” Dr. Patel explains. “It makes the vasculature in the tumor more functional, there is less hypoxia, and better blood diffusion to the tumor which makes systemic radiation and chemotherapy much more effective in killing cancer cells.”
The company marketing Nexrutine® first floated the idea of its potential in treating prostate cancer after its internal research found it dropped PSA levels in men. Dr. Kumar, who had been studying amurense for decades, then teamed up with Dr. Patel to take a closer look. “This collaboration that Dr. Kumar and I have is very synergistic,” says Dr. Patel. “He brings his expertise in tumor growth and cancer biology along with his extensive background with this product, and I bring my expertise in exercise and exercise physiology.”
Tissue slices from tumors in mouse models revealed that while amurense and exercise are equally effective in reducing inflammation in prostate cancer cells, they do so through different cell signaling pathways. Nexrutine® not only inhibited common inflammation pathways, but also promoted apoptosis (cellular suicide) in cancer cells. And, unlike aspirin, it reduced COX-2 pathway inflammation associated with several cancers without inhibiting the COX-1 enzyme, which can result in gastrointestinal problems with long-term use.
The research implies that exercise therapy combined with amurense may have up to twice the benefit hitting multiple pathways of inflammation. This next phase of human clinical trials will study the compound’s effect as a primary preventative in those at high risk for prostate cancer, a secondary preventative therapy for prostate cancer survivors, and as a tumor sensitizer for patients undergoing therapy.
Two related exercise trials will begin soon at the Mays Cancer Center. The Owens Foundation is sponsoring a trial to assess the effects of high-intensity interval training, in combination with resistance training, to improve chemotherapy tolerance and outcomes in men with metastatic prostate cancer. The Movember Foundation will sponsor a trial to assess the impact of long-term exercise in prostate cancer survivorship. Both of these studies will inform the human clinical trials with amurense as a possible alternative for those patients who cannot exercise.
Further research will determine effective dosing and establish safety profiles in healthy individuals and those with prostate cancer. But, says Dr. Patel, “as of now, there are no major safety issues that we are concerned about.”
There remains some mystery to the noble herb. While berberine and palmatine are two components of amurense clearly playing a role in its effectiveness, the extract contains many other compounds.
“Western medicine does tend to be more focused on individual mechanisms, individual proteins, and individual markers that are having an effect, whereas in Eastern and other homeopathic medicine, the focus is more of a holistic intervention.” As in exercise physiology, he suspects, all of the compounds in amurense, taken together, may have a synergistic effect. “If you could put exercise in a pill form, everyone would take it because it hits just about every pathway in our body: growth, anti-inflammatory, brain function, and so forth. Everything works together.”
“Ultimately, it’s the patient we aim to please by improving survivorship and his quality of life,” Dr. Patel says. “Just working alongside patients who are living with prostate cancer and seeing the benefits of exercise interventions is very rewarding. Now, we have the potential of Nexrutine® as a replacement therapy for those who cannot exercise or as an additional therapy for those who can. That would reduce a medical burden on our society.”