Synergistic interaction of the cannabinoid and death receptor systems - a potential target for future cancer therapies?

FEBS Lett. 2017 Oct;591(20):3235-3251. doi: 10.1002/1873-3468.12863. Epub 2017 Oct 10.

Abstract

Cannabinoid receptors have been shown to interact with other receptors, including tumor necrosis factor receptor superfamily (TNFRS) members, to induce cancer cell death. When cannabinoids and death-inducing ligands (including TNF-related apoptosis-inducing ligand) are administered together, they have been shown to synergize and demonstrate enhanced antitumor activity in vitro. Certain cannabinoid ligands have been shown to sensitize cancer cells and synergistically interact with members of the TNFRS, thus suggesting that the combination of cannabinoids with death receptor (DR) ligands induces additive or synergistic tumor cell death. This review summarizes recent findings on the interaction of the cannabinoid and DR systems and suggests possible clinical co-application of cannabinoids and DR ligands in the treatment of various malignancies.

Keywords: TNF-related apoptosis-inducing ligand; apoptosis; cancer; cannabinoid; combination therapy; death receptor.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cannabinoids / therapeutic use*
  • Drug Synergism
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Ligands
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Receptor Cross-Talk
  • Receptors, Cannabinoid / genetics*
  • Receptors, Cannabinoid / metabolism
  • Receptors, Death Domain / genetics*
  • Receptors, Death Domain / metabolism
  • Signal Transduction
  • TNF-Related Apoptosis-Inducing Ligand / therapeutic use*
  • Tumor Cells, Cultured

Substances

  • Cannabinoids
  • Ligands
  • Receptors, Cannabinoid
  • Receptors, Death Domain
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human