title: Resistance of lung cancer cells grown as multicellular tumour spheroids to zinc sulfophthalocyanine photosensitization.
abstract: 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.
authors.affiliation: Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, Doornfontein 2028, South Africa. jakonda@webmail.co.za.
authors.forename: Sello Lebohang
authors.initials: SL
authors.lastname: Manoto
authors.affiliation: Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, Doornfontein 2028, South Africa. nhoureld@uj.ac.za.
authors.forename: Nicolette Nadene
authors.initials: NN
authors.lastname: Houreld
authors.affiliation: Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, Doornfontein 2028, South Africa. habrahamse@uj.ac.za.
authors.forename: Heidi
authors.initials: H
authors.lastname: Abrahamse
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects; D049109:Cell Proliferation; D002470:Cell Survival; D006801:Humans; D007211:Indoles / Q000494:pharmacology* / Q000528:radiation effects; D007834:Lasers; D008175:Lung Neoplasms / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial; D009942:Organometallic Compounds / Q000494:pharmacology* / Q000528:radiation effects; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology* / Q000528:radiation effects; D018874:Spheroids, Cellular / Q000187:drug effects* / Q000528:radiation effects
chemical_list: D007211:Indoles; D009942:Organometallic Compounds; D011838:Radiation-Sensitizing Agents; C063072:zinc(II) phthalocyanine trisulfonic acid