Verteporfin inhibits growth of human glioma in vitro without light activation

• Published in: Scientific reports Vol. 7; no. 1; pp. 7602 - 8
• Main Authors: Al-Moujahed, Ahmad, Brodowska, Katarzyna, Stryjewski, Tomasz P., Efstathiou, Nikolaos E., Vasilikos, Ioannis, Cichy, Joanna, Miller, Joan W., Gragoudas, Evangelos, Vavvas, Demetrios G.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08.08.2017; Nature Publishing Group; Nature Portfolio
• Subjects: 13/106; 631/378; 692/699/3161; 82/29; 96/1; Adaptor Proteins, Signal Transducing - antagonists & inhibitors; Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; AKT protein; Antibodies; Axl protein; Axl Receptor Tyrosine Kinase; Brain cancer; Brain tumors; c-Myc protein; Cancer; Cancer therapies; Cell activation; Cell Line, Tumor; Cell Proliferation - drug effects; Connective tissue growth factor; Connective Tissue Growth Factor - antagonists & inhibitors; Connective Tissue Growth Factor - genetics; Connective Tissue Growth Factor - metabolism; CYR61 protein; Cysteine-Rich Protein 61 - antagonists & inhibitors; Cysteine-Rich Protein 61 - genetics; Cysteine-Rich Protein 61 - metabolism; DNA-Binding Proteins - antagonists & inhibitors; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Gene Expression Regulation, Neoplastic; Glioblastoma; Glioma; Glioma cells; Hepatocellular carcinoma; Humanities and Social Sciences; Humans; Light; MAP kinase; Medical prognosis; Membranes; Microtubule-Associated Proteins - agonists; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - metabolism; multidisciplinary; Myc protein; Neuroglia - drug effects; Neuroglia - metabolism; Neuroglia - pathology; Nuclear Proteins - antagonists & inhibitors; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Oct-4 protein; Octamer Transcription Factor-3 - antagonists & inhibitors; Octamer Transcription Factor-3 - genetics; Octamer Transcription Factor-3 - metabolism; Optic nerve; Ovarian cancer; p38 Mitogen-Activated Protein Kinases - genetics; p38 Mitogen-Activated Protein Kinases - metabolism; Phosphoproteins - antagonists & inhibitors; Phosphoproteins - genetics; Phosphoproteins - metabolism; Photodynamic therapy; Photosensitizing Agents - pharmacology; Pluripotency; Proteins; Proto-Oncogene Proteins - antagonists & inhibitors; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-myc - antagonists & inhibitors; Proto-Oncogene Proteins c-myc - genetics; Proto-Oncogene Proteins c-myc - metabolism; Receptor Protein-Tyrosine Kinases - antagonists & inhibitors; Receptor Protein-Tyrosine Kinases - genetics; Receptor Protein-Tyrosine Kinases - metabolism; Retina; Retinoblastoma; Science; Science (multidisciplinary); Signal Transduction; Survivin; Survivin - genetics; Survivin - metabolism; TEA Domain Transcription Factors; TOR protein; Transcription Factors - antagonists & inhibitors; Transcription Factors - genetics; Transcription Factors - metabolism; Tumor cell lines; Tumors; Vascular Endothelial Growth Factor A - antagonists & inhibitors; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor A - metabolism; Verteporfin - pharmacology; YAP-Signaling Proteins; Yes-associated protein
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-07632-8

Verteporfin (VP), a light-activated drug used in photodynamic therapy for the treatment of choroidal neovascular membranes, has also been shown to be an effective inhibitor of malignant cells. Recently, studies have demonstrated that, even without photo-activation, VP may still inhibit certain tumor cell lines, including ovarian cancer, hepatocarcinoma and retinoblastoma, through the inhibition of the YAP-TEAD complex. In this study, we examined the effects of VP without light activation on human glioma cell lines (LN229 and SNB19). Through western blot analysis, we identified that human glioma cells that were exposed to VP without light activation demonstrated a downregulation of YAP-TEAD-associated downstream signaling molecules, including c-myc, axl, CTGF, cyr61 and survivin and upregulation of the tumor growth inhibitor molecule p38 MAPK. In addition, we observed that expression of VEGFA and the pluripotent marker Oct-4 were also decreased. Verteporfin did not alter the Akt survival pathway or the mTor pathway but there was a modest increase in LC3-IIB, a marker of autophagosome biogenesis. This study suggests that verteporfin should be further explored as an adjuvant therapy for the treatment of glioblastoma.