Effects of zinc porphyrin and zinc phthalocyanine derivatives in photodynamic anticancer therapy under different partial pressures of oxygen in vitro
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
32833137
DOI
10.1007/s10637-020-00990-7
PII: 10.1007/s10637-020-00990-7
Knihovny.cz E-resources
- Keywords
- Hyperbaria, Photodynamic therapy, Photosensitizers,
- MeSH
- Photochemotherapy methods MeSH
- Photosensitizing Agents pharmacology MeSH
- HeLa Cells MeSH
- Indoles administration & dosage pharmacology MeSH
- Oxygen administration & dosage pharmacology MeSH
- Humans MeSH
- Membrane Potential, Mitochondrial drug effects MeSH
- Metalloporphyrins administration & dosage pharmacology MeSH
- Mitochondria drug effects MeSH
- Organometallic Compounds administration & dosage pharmacology MeSH
- Partial Pressure MeSH
- Singlet Oxygen analysis MeSH
- Cell Survival drug effects MeSH
- Dose-Response Relationship, Drug MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Photosensitizing Agents MeSH
- Indoles MeSH
- Oxygen MeSH
- Metalloporphyrins MeSH
- Organometallic Compounds MeSH
- Singlet Oxygen MeSH
- zinc phthalocyanine disulfonate MeSH Browser
- zinc tetraphenylporphyrin MeSH Browser
Photodynamic therapy (PDT) is gradually becoming an alternative method in the treatment of several diseases. Here, we investigated the role of oxygen in photodynamically treated cervical cancer cells (HeLa). The effect of PDT on HeLa cells was assessed by exposing cultured cells to disulphonated zinc phthalocyanine (ZnPcS2) and tetrasulphonated zinc tetraphenylporphyrin (ZnTPPS4). Fluorescence microscopy revealed their different localizations within the cells. ZnTPPS4 seems to be mostly limited to the cytosol and lysosomes, whereas ZnPcS2 is most likely predominantly attached to membrane structures, including plasmalemma and the mitochondrial membrane. Phototoxicity assays of PDT-treated cells carried out under different partial pressures of oxygen showed dose-dependent responses. Interestingly, ZnPcS2 was also photodynamically effective at a minimal level of oxygen, under a nitrogen atmosphere. On the other hand, hyperbaric oxygenation did not lead to a higher PDT efficiency of either photosensitizer. Although both photosensitizers can induce a significant drop in mitochondrial membrane potential, ZnPcS2 has a markedly higher effect on mitochondrial respiration that was completely blocked after two short light cycles. In conclusion, our observations suggest that PDT can be effective even in hypoxic conditions if a suitable sensitizer is chosen, such as ZnPcS2, which can inhibit mitochondrial respiration.
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