In vitro evaluation of ruthenium complexes for photodynamic therapy |
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| Affiliation: | 1. Department of Inorganic Chemistry, Faculty of Chemistry, Jagiellonian University, Ingardena 3, 30-060 Krakow, Poland;2. Université de Lorraine, CNRS, UMR SRSMC, HecRIn, Boulevard des Aiguillettes, Vandoeuvre-Lès-Nancy, France;3. Jerzy Haber Institute of Catalysis and Surface Chemistry, Polish Academy of Sciences, Niezapominajek 8, 30-239 Krakow, Poland;1. Institute of Anticancer Agents Development and Theranostic Application, The Key Laboratory of Life-Organic Analysis and Key Laboratory of Pharmaceutical Intermediates and Analysis of Natural Medicine, Department of Chemistry and Chemical Engineering, Qufu Normal University, Qufu 273165, China;2. Department of Chemistry and Chemical Engineering, Shandong Normal University, Jinan 250014, China;1. Department of Inorganic Chemistry, Faculty of Chemistry, Jagiellonian University, Ingardena 3, 30-060 Krakow, Poland;2. Institute of Organic and Analytical Chemistry, University of Orléans, UMR-CNRS 7311, rue de Chartres, BP 6759, 45067 Orléans Cedex 2, France;3. Department of Physiology, Jagiellonian University Medical College, Grzegorzecka 16, 31-531 Krakow, Poland;1. Departament de Biologia, Universitat de Girona, Maria Aurèlia Capmany 40, 17003 Girona, Spain;2. Departament de Química, Universitat de Girona, Maria Aurèlia Capmany 69, 17003 Girona, Spain;3. Universidad de Castilla-La Mancha, Facultad de Ciencias y Tecnologías Químicas-IRICA, Avda. Camilo J. Cela 10, 13071 Ciudad Real, Spain;4. Departamento de Química, Universidad de Burgos, Pza. Misael Bañuelos s/n, 09001 Burgos, Spain |
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| Abstract: | BackgroundPhotodynamic therapy (PDT) is a promising anti-tumor treatment strategy. Photosensitizer is one of the most important components of PDT. In this work, the anticancer activities of PDT mediated by six new ruthenium porphyrin complexes were screened. The mechanisms of the most efficacious candidate were investigated.MethodsPhotocytotoxicity of the six porphyrins was tested. The most promising complex, Rup-03, was further investigated using Geimsa staining, which indirectly detects reactive oxygen species (ROS) and subcellular localization. Mitochondrial membrane potential (MMP), cell apoptosis, DNA fragmentation, c-Myc gene expression, and telomerase activities were also assayed.ResultsRup-03 and Rup-04 had the lowest IC50 values. Rup-03 had an IC50 value of 29.5 ± 2.3 μM in HepG2 cells and 59.0 ± 6.1 μM in RAW264.7 cells, while Rup-04 had an IC50 value of 40.0 ± 3.8 μM in SGC-7901 cells. The complexes also induced cellular morphological changes and impaired cellular ability to scavenge ROS, and accumulated preferentially in mitochondria and endoplasmic reticulum. Rup-03 reduced MMP levels, induced apoptosis, and repressed both c-Myc mRNA expression and telomerase activity in HepG2 cells.ConclusionsAmong six candidates, Rup-03-mediated PDT is most effective against HepG2 and RAW264.7, with a similar efficacy as that of Rup-04-mediated PDT against SGC-7901 cells. Repression of ROS scavenging activities and c-Myc expression, which mediated DNA damage-induced cell apoptosis and repression of telomerase activity, respectively, were found to be involved in the anticancer mechanisms of Rup-03. |
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| Keywords: | Photodynamic therapy Ruthenium (II) complexes Porphyrin Apoptosis |
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