zinc(ii)-phthalocyanine-trisulfonic-acid and Lung-Neoplasms

Hay synthesis of a novel series of symmetrically tetra-substituted thiophenyl zinc(II)phthalocyanines (RS)

Topics: A549 Cells; Adenocarcinoma; Adenocarcinoma of Lung; Antineoplastic Agents; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Proliferation; Drug Screening Assays, Antitumor; Fibroblasts; Humans; Indoles; Inhibitory Concentration 50; Isoindoles; Lung Neoplasms; MCF-7 Cells; Molecular Structure; Organometallic Compounds; Structure-Activity Relationship; Zinc Compounds

Photodynamic therapy (PDT) is phototherapeutic modality used in the treatment of neoplastic and non-neoplastic diseases. The photochemical interaction of light, photosensitizer (PS) and molecular oxygen produces singlet oxygen which induces cell death. Zinc sulfophthalocyanine (ZnPcSmix) has been shown to be effective in A549 monolayers, multicellular tumor spheroids (MCTSs) (250 µm) and not on MCTSs with a size of 500 µm. A549 cells used in this study were grown as MCTSs to a size of 500 µm in order to determine their susceptibility to PDT. ZnPcSmix distribution in MCTSs and nuclear morphology was determined using a fluorescent microscope. Changes in cellular responses were evaluated using cell morphology, viability, proliferation, cytotoxicity, cell death analysis and mitochondrial membrane potential. Untreated MCTSs, showed no changes in cellular morphology, proliferation, cytotoxicity and nuclear morphology. Photoactivated ZnPcSmix also showed no changes in cellular morphology and nuclear morphology. However, photoactivated ZnPcSmix resulted in a significant dose dependant decrease in viability and proliferation as well as an increase in cell membrane damage in MCTSs over time. ZnPcSmix photosensitization induces apoptotic cell death in MCTSs with a size of 500 µm and more resistantance when compared to monolayer cells and MCTSs with a size of 250 µm.

Topics: Apoptosis; Cell Line, Tumor; Cell Membrane; Cell Nucleus; Cell Proliferation; Cell Survival; Humans; Indoles; Lasers; Lung Neoplasms; Membrane Potential, Mitochondrial; Organometallic Compounds; Radiation-Sensitizing Agents; Spheroids, Cellular

Photodynamic therapy (PDT) is a therapeutic modality used for treating cancerous cells. It has been previously shown that mixed sulfonated metallophthalocyanine complex, zinc sulfophthalocyanine (ZnPcS(mix)) is effective in destroying lung cancer cells. This study aimed to determine subcellular localization of ZnPcS(mix) and its effect on two cancer cell lines.. ZnPcS(mix) was activated at a wavelength of 680 nm with 5 J/cm². Colon (DLD-1) and lung (A549) cancer cell lines were used. Subcellular localization of ZnPcS(mix) was determined by fluorescence microscopy. Toxicity of PS alone and combination of light and PS (PDT) was determined by cell morphology, viability, proliferation and cytotoxicity. Cells which received no irradiation (0 J/cm²), irradiation alone (5 J/cm²) or treated with PS alone (no irradiation) served as controls.. ZnPcS(mix) localized in both lysozomes and mitochondria in both A549 and DLD-1 cells. A549 cells treated with PDT showed a significant decrease in viability and proliferation in all PS concentrations used, while in DLD-1 cells a significant decrease was seen with concentrations of 10, 20 and 40 μM. In absence of light, ZnPcS(mix) did not result in cellular toxicity in A549 cells whereas in DLD-1 cells it resulted in a reduction in cell proliferation only at a concentration of 40 μM.. ZnPcS(mix) was effective in inducing cell death in both cell lines when localized in vital organelles such mitochondria and lysozomes which are essential for cell functioning. Photoactivated ZnPcS(mix) affected the cells at different concentration and yielded good therapeutic results in vitro.

Topics: Adenocarcinoma; Cell Death; Cell Line, Tumor; Cell Proliferation; Colonic Neoplasms; Dose-Response Relationship, Drug; Humans; Indoles; Lung Neoplasms; Mitochondria; Organometallic Compounds; Photochemotherapy; Photosensitizing Agents

Photodynamic therapy (PDT) is a photochemotherapeutic process that is used for the treatment of cancer. Photofrin is the most widely used photosensitizer, however, the chemical composition of Photofrin is unclear and it has a low absorption in the therapeutic wavelength (600-900 nm). This factor has stimulated research in synthesis and testing of new photosensitizers. This in vitro study evaluated the effectiveness of a Zn sulfophthalocyanine (ZnPcS(mix)) as a potential photosensitizer in the treatment of human lung cancer. Lung cancer cells (A549) were divided into four groups: group 1 was control cells receiving neither light nor drug; group 2 was light control for cells exposed to laser irradiation at a fluence of 4.98 J/cm(2); group 3 was drug control for cells incubated with 15.8 μM photosensitizer and not exposed to laser irradiation, while group 4 was cells receiving the experimental treatment with 15.8 μM photosensitizer and irradiation with 4.98 J/cm(2). Laser irradiations were performed using a 636-nm diode laser with an output power of 110 mW at 4.98 J/cm(2). Changes in cellular responses were evaluated by cell morphology, viability, proliferation, and cytotoxicity. While control groups 1, 2, and 3 showed no changes in cell morphology, viability, proliferation, or cytotoxicity, group 4 receiving both photosensitizer and irradiation showed changes in cell morphology, a decrease in cell viability and proliferation, and an increase in cytotoxicity, cell death, and cell membrane damage. Irradiation or photosensitizer alone had no effect on the lung cancer cells since the cells remained viable and showed no evidence of damage. However, irradiation in the presence of a photosensitizer induced cell death.

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Analysis of Variance; Cell Proliferation; Cell Survival; Cells, Cultured; Hematoporphyrin Derivative; Humans; Indoles; Low-Level Light Therapy; Lung Neoplasms; Organometallic Compounds; Photochemotherapy; Photosensitizing Agents