Indian long pepper is a plant that is commonly used in combination with other herbs in Ayurvedic medicine and other types of traditional medicine. The traditional herb goes by the botanical name Piper longum and comes from the Piperaceae family. Indian long pepper has been used for gastrointestinal problems, lung problems, arthritis, menstruation, and many other conditions, but there is no scientific evidence to support these uses.

Piperlongumine, a chemical compound found in the Indian long pepper plant has been known to kill cancerous cells in many tumor types, including brain tumors. Now, new research by an international team including researchers from the Perelman School of Medicine at the University of Pennsylvania has shed light on one way in which piperlongumine works against glioblastoma in animal models.

Their findings are published in the journal ACS Central Science in a paper titled, “Allosteric Antagonist Modulation of TRPV2 by Piperlongumine Impairs Glioblastoma Progression.”

“Natural products provide ample opportunities to develop innovative medicines,” wrote the researchers. “However, understanding their mechanisms of action remains a bottleneck to unlock their promise in drug discovery. Chemoproteomics is a privileged approach to unveil new biology for molecules of therapeutic interest. However, such methods are laborious and time-consuming and unlikely identify membrane proteins and targets with only minute expression.”

The researchers demonstrate how piperlongumine binds and hinders the activity of a protein called TRPV2. TRPV2 has been shown to be a cancer biomarker and novel therapeutic target. The protein is implicated in signaling pathways that mediate cell survival, proliferation, and metastasis.

“This study gives us a much clearer picture of how piperlongumine works against glioblastoma, and in principle enables us to develop treatments that can be even more potent,” explained study co-senior author Vera Moiseenkova-Bell, PhD, an associate professor of pharmacology and faculty director of the Electron Microscopy Resource Laboratory and Beckman Center for Cryo Electron Microscopy at Penn Medicine.

Cancers such as glioblastoma are difficult to treat because drug molecules that cross from the bloodstream into the brain are needed. The researchers developed a hydrogel-type scaffold that could be filled with piperlongumine and implanted. In two different glioblastoma mouse models, they demonstrated that their piperlongumine-filled scaffold destroyed the glioblastomas almost completely and greatly extended mouse survival compared to untreated mice. They also observed similar results against glioblastoma cells from human patients.

The researchers are now working to move their strategy forward to further preclinical studies. They are also studying molecular TRPV2 further.

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