The clinically used photosensitizer Verteporfin (VP) inhibits YAP-TEAD and human retinoblastoma cell growth in vitro without light activation
Open accessAbstract
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.
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A number of inhibitors targeting YAP/TAZ-TEAD have been reported, including peptides such as super-TDU, and small molecules such as verteporfin and MGH-CP1.
“Over the years, a number of inhibitors targeting YAP/TAZ-TEAD have been reported, including peptides such as super-TDU (173),437 and small molecules such as verteporfin (174) and MGH-CP1 (175).438–440”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [440]
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- Authors
- Brodowska, K., Al-Moujahed, A., Marmalidou, A., Meyer zu Horste, M., Cichy, J., Miller, J. W., Gragoudas, E., & Vavvas, D. G.
- Affiliations
- Massachusetts Eye and Ear Infirmary (US)
- Jagiellonian University (PL)
- Corresponding author
- Vavvas, Demetrios G.
- Venue
- Experimental Eye Research
- Publisher
- Elsevier BV
- Published
- 2014-07
- Volume
- 124
- Pages
- 67-73
- ISSN
- 0014-4835 (ISSN-L)
- PMC
- PMC4135181
- OpenAlex
- W2060073863
- Cited by
- 220
- References
- 63
- Citations by year
- 2026: 9 · 2025: 10 · 2024: 12 · 2023: 21 · 2022: 23 · 2021: 21 · 2020: 24 · 2019: 28 · 2018: 23 · 2017: 20 · 2016: 15 · 2015: 11 · 2014: 3
- FWCI
- 8.30
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Experimental Eye Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Jagiellonian University Repository (Jagiellonian University) (submittedVersion, cc-by-nc-nd)
- Funders
- National Eye Institute (R21EY023079)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
- Health Sciences › Medicine › Ophthalmology › Ocular Oncology and Treatments
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Photodynamic Therapy Research Studies
- Keywords
- verteporfin, retinoblastoma, photosensitizers, cell proliferation, Oct4, c-Myc, AXL, VEGF-A, angiogenesis, connective tissue growth factor, CYR61, adjuvant therapy
- MeSH terms
- Verteporfin, Child, Preschool, Dose-Response Relationship, Drug, Follow-Up Studies, Humans, Infant, Infant, Newborn, Photochemotherapy, Porphyrins, Retina, Retinoblastoma, Tumor Cells, Cultured, Photosensitizing Agents, Retinal Neoplasms, Cell Proliferation
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