Piperlongumine, a chemical compound found in the Indian Long Pepper plant (Piper longum), is known to kill cancerous cells in many tumor types, including brain tumors. Now, an international team including researchers from the Perelman School of Medicine has illuminated one way in which the piperlongumine works in animal models—and has confirmed its strong activity against glioblastoma, one of the least treatable types of brain cancer.

The researchers, whose findings were published this month in ACS Central Science, showed in detail how piperlongumine binds to—and hinders the activity of—a protein called TRPV2, which is overexpressed in glioblastoma in a way that appears to drive cancer progression. The scientists found that piperlongumine treatment radically shrank glioblastoma tumors and extended life in two animal models of this cancer, and also selectively destroyed glioblastoma cells taken from human patients.

“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,” said study co-senior author Vera Moiseenkova-Bell, an associate professor of pharmacology and faculty director of the Electron Microscopy Resource Laboratory and Beckman Center for Cryo Electron Microscopy at Penn Medicine.

The researchers are now working to develop their approach in further preclinical studies, with the hope of one day testing it in clinical trials with glioblastoma patients. In addition, Moiseenkova-Bell’s structural findings will enable the researchers to experiment with piperlongumine and modified versions of it to develop an even stronger and more selective inhibitor of TRPV2.