The clinically used photosensitizer Verteporfin (VP) inhibits YAP-TEAD and human retinoblastoma cell growth in vitro without light activation.
2014
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 hrough inhibition of YAP-TEAD complex. In this study, we examined the effects of VP without light activation on human
retinoblastomacell lines.
Verteporfinbut not vehicle control inhibited the growth, proliferation and viability of human
retinoblastomacell 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
Verteporfintreatment. Our results indicate that the clinically used photosensitizer VP is a potent inhibitor of cell growth in
retinoblastoma
cells,
disruptingYAPTEAD signaling and pluripotential marker OCT4. This study highlights for the first time the role of the YAP-TEAD pathway in
Retinoblastomaand suggests that VP may be a useful adjuvant therapeutic tool in treating Rb patients.
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