Capsaicin-induced apoptosis of glioma cells is mediated by TRPV1 vanilloid receptor and requires p38 MAPK activation

J Neurochem. 2007 Aug;102(3):977-90. doi: 10.1111/j.1471-4159.2007.04582.x. Epub 2007 Apr 17.


We provide evidence on the expression of the transient receptor potential vanilloid type-1 (TRPV1) by glioma cells, and its involvement in capsaicin (CPS)-induced apoptosis. TRPV1 mRNA was identified by quantitative RT-PCR in U373, U87, FC1 and FLS glioma cells, with U373 cells showing higher, and U87, FC1 and FLS cells lower TRPV1 expression as compared with normal human astrocytes. By flow cytometry we found that a substantial portion of both normal human astrocytes, and U87 and U373 glioma cells express TRPV1 protein. Moreover, we analyzed the expression of TRPV1 at mRNA and protein levels of glioma tissues with different grades. We found that TRPV1 gene and protein expression inversely correlated with glioma grading, with marked loss of TRPV1 expression in the majority of grade IV glioblastoma multiforme. We also described that CPS trigger apoptosis of U373, but not U87 cells. CPS-induced apoptosis involved Ca(2+) influx, p38 but not extracellular signal-regulated mitogen-activated protein kinase activation, phosphatidylserine exposure, mitochondrial permeability transmembrane pore opening and mitochondrial transmembrane potential dissipation, caspase 3 activation and oligonucleosomal DNA fragmentation. TRPV1 was functionally implicated in these events as they were markedly inhibited by the TRPV1 antagonist, capsazepine. Finally, p38 but not extracellular signal-regulated protein kinase activation was required for TRPV1-mediated CPS-induced apoptosis of glioma cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Astrocytes / metabolism
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / physiopathology
  • Calcium Signaling / drug effects
  • Calcium Signaling / physiology
  • Capsaicin / pharmacology*
  • Caspase 3 / drug effects
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Enzyme Activation / drug effects
  • Enzyme Activation / physiology
  • Gene Expression Regulation, Neoplastic / physiology
  • Glioblastoma / genetics
  • Glioblastoma / metabolism
  • Glioblastoma / physiopathology
  • Glioma / drug therapy
  • Glioma / metabolism*
  • Glioma / physiopathology
  • Humans
  • Membrane Potential, Mitochondrial / drug effects
  • Membrane Potential, Mitochondrial / genetics
  • RNA, Messenger / drug effects
  • RNA, Messenger / metabolism
  • TRPV Cation Channels / drug effects
  • TRPV Cation Channels / genetics
  • TRPV Cation Channels / metabolism*
  • p38 Mitogen-Activated Protein Kinases / drug effects
  • p38 Mitogen-Activated Protein Kinases / metabolism*


  • Antineoplastic Agents
  • RNA, Messenger
  • TRPV Cation Channels
  • TRPV1 protein, human
  • p38 Mitogen-Activated Protein Kinases
  • Caspase 3
  • Capsaicin