Necrotic and apoptotic cell death of human malignant melanoma cells following photodynamic therapy using an amphiphilic photosensitizer, ATX‐S10(Na)
- 9 July 2003
- journal article
- research article
- Published by Wiley in Lasers in Surgery and Medicine
- Vol. 33 (1), 64-70
- https://doi.org/10.1002/lsm.10190
Abstract
Background and Objectives To investigate the phototoxic effect on and cell death modes of human malignant melanoma cells following photodynamic therapy (PDT) using ATX-S10(Na), an amphiphilic photosensitizer. Materials and Methods Cultured human malignant melanoma cells were incubated in a medium containing various concentrations of ATX-S10(Na) and irradiated with a 670 nm wavelength diode laser. Phototoxicity was analyzed by a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt (MTS) assay, and cell death modes were investigated by fluorescence microscopy using a Hoechst 33342-propidium iodide double-staining method as well as by static gel electrophoresis. The subcellular localization of ATX-S10(Na) and mitochondrial destabilization following PDT were observed by fluorescence microscopy. Results Higher phototoxicity was obtained with higher dye and/or laser doses. Most of the dead cells appeared apoptotic with dye and irradiation doses that induced less than 70% cytotoxicity. In contrast, most of them appeared necrotic with doses that induced 99% cytotoxicity. Cells receiving PDT showed disturbances of mitochondrial trans-membrane potential, although the primary site of ATX-S10(Na) accumulation was in lysosomes. Conclusions ATX-S10(Na) has a phototoxic effect on malignant melanoma cells and, therefore, potential as a photosensitizing agent for PDT designed to kill these cells. Apoptotic pathways may be activated via mitochondrial destabilization following the damage of lysosomes by PDT. Further study, including investigation of therapeutic efficacy in vivo, is warranted. Lasers Surg. Med. 33:64–70, 2003.Keywords
This publication has 39 references indexed in Scilit:
- Determinants of the Apoptotic Response to Lysosomal PhotodamagePhotochemistry and Photobiology, 2007
- Subcellular Localization of Merocyanine 540 (MC540) and Induction of Apoptosis in Murine Myeloid Leukemia Cells ¶Photochemistry and Photobiology, 2007
- In vitro Plasma Protein Binding and Cellular Uptake of ATX‐S10(Na), a Hydrophilic Chlorin PhotosensitizerJapanese Journal of Cancer Research, 2000
- Photodynamic Therapy for Experimental Tumors Using ATX-S10(Na), a Hydrophilic Chlorin Photosensitizer, and Diode LaserJapanese Journal of Cancer Research, 2000
- Light-induced Apoptosis Involves a Defined Sequence of Cytoplasmic and Nuclear Calcium Release in AlPcS4-photosensitized Rat Bladder RR 1022 Epithelial Cells¶Photochemistry and Photobiology, 2000
- Enhanced Responsiveness to Photodynamic Therapy-Induced Apoptosis after Mitochondrial DNA DepletionPhotochemistry and Photobiology, 1999
- Photodynamic Therapy-Induced Apoptosis in Lymphoma Cells: Translocation of Cytochrome c Causes Inhibition of Respiration as Well as Caspase ActivationBiochemical and Biophysical Research Communications, 1999
- Apoptosis or Necrosis Following Photofrin® Photosensitization: Influence of the Incubation ProtocolPhotochemistry and Photobiology, 1996
- Rapid Initiation of Apoptosis by Photodynamic TherapyPhotochemistry and Photobiology, 1996
- Photodynamic therapy: a 5-year study of its effectiveness in the treatment of posterior uveal melanoma, and evaluation of haematoporphyrin uptake and photocytotoxicity of melanoma cells in tissue cultureMelanoma Research, 1995