Verteporfin-induced formation of protein cross-linked oligomers and high molecular weight complexes is mediated by light and leads to cell toxicity

Eleni K. Konstantinou, Shoji Notomi, Cassandra Kosmidou, Katarzyna Brodowska, Ahmad Al-Moujahed, Fotini Nicolaou, Pavlina Tsoka, Evangelos Gragoudas, Joan W. Miller, Lucy H. Young, Demetrios G. Vavvas

Research output: Contribution to journalArticle

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Abstract

Verteporfin (VP) was first used in Photodynamic therapy, where a non-thermal laser light (689 nm) in the presence of oxygen activates the drug to produce highly reactive oxygen radicals, resulting in local cell and tissue damage. However, it has also been shown that Verteporfin can have non-photoactivated effects such as interference with the YAP-TEAD complex of the HIPPO pathway, resulting in growth inhibition of several neoplasias. More recently, it was proposed that, another non-light mediated effect of VP is the formation of cross-linked oligomers and high molecular weight protein complexes (HMWC) that are hypothesized to interfere with autophagy and cell growth. Here, in a series of experiments, using human uveal melanoma cells (MEL 270), human embryonic kidney cells (HEK) and breast cancer cells (MCF7) we showed that Verteporfin-induced HMWC require the presence of light. Furthermore, we showed that the mechanism of this cross-linking, which involves both singlet oxygen and radical generation, can occur very eficiently even after lysis of the cells, if the lysate is not protected from ambient light. This work offers a better understanding regarding VP's mechanisms of action and suggests caution when one studies the non-light mediated actions of this drug.

Original languageEnglish
Article number46581
JournalScientific reports
Volume7
DOIs
Publication statusPublished - Jan 1 2017
Externally publishedYes

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Oligomers
Toxicity
Molecular weight
Reactive Oxygen Species
Proteins
Singlet Oxygen
Photodynamic therapy
Cell growth
Pharmaceutical Preparations
Cells
Tissue
Oxygen
verteporfin
Lasers
Experiments

All Science Journal Classification (ASJC) codes

  • General

Cite this

Verteporfin-induced formation of protein cross-linked oligomers and high molecular weight complexes is mediated by light and leads to cell toxicity. / Konstantinou, Eleni K.; Notomi, Shoji; Kosmidou, Cassandra; Brodowska, Katarzyna; Al-Moujahed, Ahmad; Nicolaou, Fotini; Tsoka, Pavlina; Gragoudas, Evangelos; Miller, Joan W.; Young, Lucy H.; Vavvas, Demetrios G.

In: Scientific reports, Vol. 7, 46581, 01.01.2017.

Research output: Contribution to journalArticle

Konstantinou, EK, Notomi, S, Kosmidou, C, Brodowska, K, Al-Moujahed, A, Nicolaou, F, Tsoka, P, Gragoudas, E, Miller, JW, Young, LH & Vavvas, DG 2017, 'Verteporfin-induced formation of protein cross-linked oligomers and high molecular weight complexes is mediated by light and leads to cell toxicity', Scientific reports, vol. 7, 46581. https://doi.org/10.1038/srep46581
Konstantinou, Eleni K. ; Notomi, Shoji ; Kosmidou, Cassandra ; Brodowska, Katarzyna ; Al-Moujahed, Ahmad ; Nicolaou, Fotini ; Tsoka, Pavlina ; Gragoudas, Evangelos ; Miller, Joan W. ; Young, Lucy H. ; Vavvas, Demetrios G. / Verteporfin-induced formation of protein cross-linked oligomers and high molecular weight complexes is mediated by light and leads to cell toxicity. In: Scientific reports. 2017 ; Vol. 7.
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