This work presents results on the efficiency of newly designed zinc phthalocyanine-mediated photodynamic therapy of both tumoral and nontumoral cell models using the MTT assay. Further detailed examinations of mechanistic and cell biological effects were focused on the HELA cervical cancer cell model. Here, ROS production, changes in the mitochondrial membrane potential, the determination of genotoxicity, and protein changes determined by capillary chromatography and tandem mass spectrometry with ESI were analyzed. The results showed that, in vitro, 5 Jcm-2 ZnPc PDT caused a significant increase in reactive oxygen species. Still, except for superoxide dismutase, the levels of proteins involved in cell response to oxidative stress did not increase significantly. Furthermore, this therapy damaged mitochondrial membranes, which was proven by a more than 70% voltage-dependent channel protein 1 level decrease and by a 65% mitochondrial membrane potential change 24 h post-therapy. DNA impairment was assessed by an increased level of DNA fragmentation, which might be related to the decreased level of DDB1 (decrease in levels of more than 20% 24 h post-therapy), a protein responsible for maintaining genomic integrity and triggering the DNA repair pathways. Considering these results and the low effective concentration (LC50 = 30 nM), the therapy used is a potentially very promising antitumoral treatment.

• MeSH
• fotochemoterapie * metody   MeSH
• fotosenzibilizující látky * farmakologie   chemie   MeSH
• HeLa buňky MeSH
• indoly * farmakologie   chemie   MeSH
• isoindoly * MeSH
• lidé MeSH
• membránový potenciál mitochondrií * účinky léků   MeSH
• organokovové sloučeniny * farmakologie   chemie   MeSH
• oxidační stres účinky léků   MeSH
• poškození DNA účinky léků   MeSH
• reaktivní formy kyslíku * metabolismus   MeSH
• sloučeniny zinku * farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND/AIM: Colorectal cancer (CRC) is one of the most widespread malignancies. One of the alternative therapeutic methods appears to be photodynamic therapy (PDT). MATERIALS AND METHODS: This study investigated the efficiency of 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin zinc (ZnTPPS4) and chloro-aluminum phthalocyanine disulfonate (ClAlPcS2) with two commercial photosensitive compounds 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphyrin (TMPyP) and tetramethylthionine chloride (methylene blue, MB) in PDT for CRC in vitro. In addition to the study of the photodynamic effect on the viability of the colorectal carcinoma cell line HT29, cellular uptake, ROS production, and DNA damage were investigated. RESULTS: All photosensitizers showed good accumulation within HT29 cells, high efficiency in killing the cells, and a concentration-dependent increase in the production of ROS. CONCLUSION: PDT using ZnTPPS4 and ClAlPcS2 may be effective in the treatment of CRC, achieving a similar photocytotoxic effect at much lower concentrations compared to MB.

• MeSH
• adenokarcinom * farmakoterapie   metabolismus   patologie   MeSH
• buňky HT-29 MeSH
• fotochemoterapie * metody   MeSH
• fotosenzibilizující látky * farmakologie   MeSH
• indoly * farmakologie   MeSH
• kolorektální nádory * farmakoterapie   patologie   metabolismus   MeSH
• lidé MeSH
• metaloporfyriny * farmakologie   MeSH
• organokovové sloučeniny * farmakologie   MeSH
• poškození DNA účinky léků   MeSH
• reaktivní formy kyslíku * metabolismus   MeSH
• viabilita buněk účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH