Cannabinoid CB2 receptor as a new phototherapy target for the inhibition of tumor growth

Mol Pharm. 2014 Jun 2;11(6):1919-29. doi: 10.1021/mp5001923. Epub 2014 May 8.

Abstract

The success of targeted cancer therapy largely relies upon the selection of target and the development of efficient therapeutic agents that specifically bind to the target. In the current study, we chose a cannabinoid CB2 receptor (CB2R) as a new target and used a CB2R-targeted photosensitizer, IR700DX-mbc94, for phototherapy treatment. IR700DX-mbc94 was prepared by conjugating a photosensitizer, IR700DX, to mbc94, whose binding specificity to CB2R has been previously demonstrated. We found that phototherapy treatment using IR700DX-mbc94 greatly inhibited the growth of CB2R positive tumors but not CB2R negative tumors. In addition, phototherapy treatment with nontargeted IR700DX did not show significant therapeutic effect. Similarly, treatment with IR700DX-mbc94 without light irradiation or light irradiation without the photosensitizer showed no tumor-inhibitory effect. Taken together, IR700DX-mbc94 is a promising phototherapy agent with high target-specificity. Moreover, CB2R appears to have great potential as a phototherapeutic target for cancer treatment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Indoles / pharmacology*
  • Mice
  • Neoplasms / drug therapy*
  • Organosilicon Compounds / pharmacology*
  • Photosensitizing Agents / pharmacology*
  • Phototherapy / methods
  • Receptor, Cannabinoid, CB2 / metabolism*

Substances

  • IR700DX-mbc94
  • Indoles
  • Organosilicon Compounds
  • Photosensitizing Agents
  • Receptor, Cannabinoid, CB2