The Clinically Used Photosensitizer Verteporfin (VP) Inhibits YAP-TEAD and Human Retinoblastoma Cell Growth in Vitro Without Light Activation

Exp Eye Res. 2014 Jul;124:67-73. doi: 10.1016/j.exer.2014.04.011. Epub 2014 May 15.

Abstract

Verteporfin (VP), a benzoporphyrin derivative, is clinically used in photodynamic therapy for neovascular macular degeneration. Recent studies indicate that VP may inhibit growth of hepatoma cells without photoactivation through inhibition of YAP-TEAD complex. In this study, we examined the effects of VP without light activation on human retinoblastoma cell lines. Verteporfin but not vehicle control inhibited the growth, proliferation and viability of human retinoblastoma cell lines (Y79 and WERI) in a dose-dependent manner and was associated with downregulation of YAP-TEAD associated downstream proto-oncogenes such as c-myc, Axl, and surviving. In addition VP affected signals involved in cell migration and angiogenesis such as CTGF, cyr61, and VEGF-A but was not associated with significant effect on the mTOR/autophagy pathway. Of interest the pluripotency marker Oct4 were downregulated by Verteporfin treatment. Our results indicate that the clinically used photosensitizer VP is a potent inhibitor of cell growth in retinoblastoma cells, disrupting YAP-TEAD signaling and pluripotential marker OCT4. This study highlights for the first time the role of the YAP-TEAD pathway in Retinoblastoma and suggests that VP may be a useful adjuvant therapeutic tool in treating Rb patients.

Keywords: Hippo; Oct4; YAP; cancer; eye; intraocular.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Proliferation / drug effects
  • Child, Preschool
  • Dose-Response Relationship, Drug
  • Follow-Up Studies
  • Humans
  • Infant
  • Infant, Newborn
  • Photochemotherapy / methods*
  • Photosensitizing Agents / administration & dosage
  • Photosensitizing Agents / therapeutic use
  • Porphyrins / administration & dosage
  • Porphyrins / therapeutic use*
  • Retina / drug effects
  • Retina / pathology*
  • Retinal Neoplasms / drug therapy*
  • Retinal Neoplasms / pathology
  • Retinoblastoma / drug therapy*
  • Retinoblastoma / pathology
  • Tumor Cells, Cultured
  • Verteporfin

Substances

  • Photosensitizing Agents
  • Porphyrins
  • Verteporfin