The chemical process behind anti-cancer properties in a spicy Indian pepper plant called the long pepper, whose suspected medicinal properties date back thousands of years, has been revealed by scientists at UT Southwestern Medical Center.

The key lies in a chemical called piperlongumine (PL), which has shown activity against many cancers including lung, colon, breast, prostate, lymphoma, leukemia, primary brain tumors, and gastric cancer.

Using x-ray crystallography, researchers were able to create molecular structures that show how the chemical is transformed after being ingested.

Piperlongumine converts to hPL, an active drug that silences a gene called GSTP1. The GSTP1 gene produces a detoxification enzyme that is often overly abundant in tumors.

The Long Pepper

Dr. Kenneth Westover, Assistant Professor of Biochemistry and Radiation Oncology, said:

“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. This research is a spectacular demonstration of the power of x-ray crystallography."

[caption id=“attachment_85791” align=“alignright” width=“285”]Long pepper Long pepper (Piper longum) was first referenced in ancient Ayurvedic textbooks, where medicinal and dietary uses were described. Source: National Institutes of Health[/caption]

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.

“This study illustrates the importance of examining and re-examining our theories. In this case we learned something fundamentally new about a 3,000-year-old medical claim using modern science,” said Dr. Westover.

X-ray crystallography allows scientists to determine molecular structures that reveal how molecules interact with targets - in this case how PL interacts with GSTP1. Viewing the structures helps in developing drugs for those targets.

The work was supported by the V Foundation for Cancer Research, The Welch Foundation, and the Cancer Prevention and Research Institute of Texas.

The study is published in the Journal of Biological Chemistry.

Top Image: molecular model of piperlongumine. Credit: UT Southwestern

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