The anti-hypertensive drug prazosin inhibits glioblastoma growth via the PKCδ-dependent inhibition of the AKT pathway

EMBO Mol Med. 2016 May 2;8(5):511-26. doi: 10.15252/emmm.201505421. Print 2016 May.


A variety of drugs targeting monoamine receptors are routinely used in human pharmacology. We assessed the effect of these drugs on the viability of tumor-initiating cells isolated from patients with glioblastoma. Among the drugs targeting monoamine receptors, we identified prazosin, an α1- and α2B-adrenergic receptor antagonist, as the most potent inducer of patient-derived glioblastoma-initiating cell death. Prazosin triggered apoptosis of glioblastoma-initiating cells and of their differentiated progeny, inhibited glioblastoma growth in orthotopic xenografts of patient-derived glioblastoma-initiating cells, and increased survival of glioblastoma-bearing mice. We found that prazosin acted in glioblastoma-initiating cells independently from adrenergic receptors. Its off-target activity occurred via a PKCδ-dependent inhibition of the AKT pathway, which resulted in caspase-3 activation. Blockade of PKCδ activation prevented all molecular changes observed in prazosin-treated glioblastoma-initiating cells, as well as prazosin-induced apoptosis. Based on these data, we conclude that prazosin, an FDA-approved drug for the control of hypertension, inhibits glioblastoma growth through a PKCδ-dependent mechanism. These findings open up promising prospects for the use of prazosin as an adjuvant therapy for glioblastoma patients.

Keywords: GL261; glioma; rottlerin; sh PKCδ; δV1.1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antihypertensive Agents / pharmacology
  • Antineoplastic Agents / pharmacology*
  • Apoptosis
  • Cell Survival / drug effects
  • Disease Models, Animal
  • Drug Repositioning*
  • Glioblastoma / drug therapy*
  • Heterografts
  • Humans
  • Mice
  • Oncogene Protein v-akt / metabolism*
  • Prazosin / pharmacology*
  • Protein Kinase C-delta / metabolism*
  • Signal Transduction*
  • Survival Analysis


  • Antihypertensive Agents
  • Antineoplastic Agents
  • Prkcd protein, mouse
  • Oncogene Protein v-akt
  • Protein Kinase C-delta
  • Prazosin