Ingredient in Indian Long Pepper Shows Promise Against Glioblastoma in Animal Models; Cryo-EM Illuminates Mechanism of Action; Piperlongumine Allosterically Inhibits TRPV2 Ion Channel Overexpressed in Glioblastoma

Piperlongumine, a chemical compound found in the Indian Long Pepper plant (Piper longum) (photo), 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 at the University of Pennsylvania 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 online on April 14, 2021 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 mouse models of this cancer, and also selectively destroyed glioblastoma cells taken from human patients. The open-access article is titled “Allosteric Antagonist Modulation of TRPV2 by Piperlongumine Impairs Glioblastoma Progression” ( "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, 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. The study was a collaboration led by the laboratory of co-senior author Gonçalo J. L. Bernardes, DPhil, of the Institute of Molecular Medicine, University of Lisbon and the University of Cambridge. "We are thrilled with the prospect of bringing our findings from bench to bedside to make a real impact on the health of people suffering from this horrendous disease," Dr. Bernardes said.
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