Researchers Uncover Mechanism for Cancer-Killing Properties of Indian Pepper Plant; Work Is “Spectacular Demonstration of the Power of X-Ray Crystallography”

University of Texas (UT) Southwestern Medical Center scientists have uncovered the chemical process behind anti-cancer properties of a spicy Indian pepper plant called the long pepper, for which suspicions of medicinal properties date back thousands of years. The secret lies in a chemical called piperlongumine (PL), which has shown activity against many cancers including prostate, breast, lung, colon, lymphoma, leukemia, primary brain tumors, and gastric cancer. Using x-ray crystallography, UTSMC researchers were able to create molecular structures that show how the chemical is transformed after being ingested. PL is converted to hPL (hydrolyzed PL), an active drug that silences a gene called GSTP1. The GSTP1 gene produces a detoxification enzyme that is often overly abundant in tumors. “We are hopeful that our structure will enable additional drug development efforts to improve the potency of PL for use in a wide range of cancer therapies,” said Kenneth Westover (photo), M.D., Ph.D., Assistant Professor of Biochemistry and Radiation Oncology. “This research is a spectacular demonstration of the power of x-ray crystallography.” The long pepper, a plant native to India, is found in southern India and southeast Asia. Although rare in European fare, it is commonly found in Indian stores and used as a spice or seasoning in stews and other dishes. It dates back thousands of years in the Indian subcontinent tied to Ayurveda, one of the world’s oldest medical systems, and was referred to by Hippocrates, the ancient Greek physician known as the father of medicine.
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