Signal transduction and metabolic changes during tumor cell apoptosis following phthalocyanine-sensitized photodynamic therapy

Nancy L. Oleinick; Munna L. Agarwal; Nathan A. Berger M.D.; Ming-Feng Cheng; Satadel Chatterjee; Jin He; Malcolm E. Kenney; Hedy E. Larkin; Hasan Mukhter; Boris D. Rihter; Syed I. A. Zaidi

doi:10.1117/12.146317

18 June 1993 Signal transduction and metabolic changes during tumor cell apoptosis following phthalocyanine-sensitized photodynamic therapy

Nancy L. Oleinick, Munna L. Agarwal, Nathan A. Berger M.D., Ming-Feng Cheng, Satadel Chatterjee, Jin He, Malcolm E. Kenney, Hedy E. Larkin, Hasan Mukhter, Boris D. Rihter, Syed I. A. Zaidi

Author Affiliations +

Proceedings Volume 1881, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy II; (1993) https://doi.org/10.1117/12.146317
Event: OE/LASE'93: Optics, Electro-Optics, and Laser Applications in Scienceand Engineering, 1993, Los Angeles, CA, United States

Abstract

Mechanisms of cell death have been explored in cells and tumors treated with photodynamic therapy (PDT). Photosensitizers used for these studies were Photofrin, tetrasulfonated and nonsulfonated aluminum phthalocyanine, and a new silicon phthalocyanine [SiPc(OH)OSi(CH₃)₂(CH₂)₃N(CH₃)₂], referred to as PcIV. In mouse lymphoma L5178Y cells, a dose of PDT sensitized by PcIV which causes a 90% loss of cell survival induces apoptosis (programmed cell death) over a several-hour time course, beginning within 10 minutes of irradiation. Apoptosis is a metabolic process initiated by PDT-induced damage to membranes and triggered by the activation of phospholipases A₂ and C and the release of Ca⁺⁺ from intracellular stores. An endogenous endonuclease is activated and cleaves nuclear DNA in the internucleosomal region of chromatin. Subsequent metabolic events now appear to cause the loss of cellular NAD and ATP, the former a result of the activation of a second nuclear enzyme, poly(ADP-ribose) polymerase, by the endonucleolytically generated DNA strand breaks. Loss of ATP follows upon the loss of NAD needed for energy metabolism. Although the induction of apoptosis is efficiently produced by direct PDT damage to L5178Y cells, we now find that apoptosis is also produced by treatment of certain other lymphoid-derived cells and cells of epithelial origin. Under the limited set of conditions tested, there was no evidence for PDT-induced apoptosis in a fibroblast cell line, in mouse fibrosarcoma RIF-1 and L929 cells, in human adenocarcinoma A549 cells, or in human squamous cell carcinoma cells in culture. The evidence suggests that apoptosis, a form of metabolic cell death, is an important mechanism of tumor ablation in PDT-treated tumors, and that the induction of apoptosis may involve the interaction of direct PDT damage to malignant cells with factors produced by PDT action on vascular and other host cells.

Citation Download Citation

Nancy L. Oleinick, Munna L. Agarwal, Nathan A. Berger M.D., Ming-Feng Cheng, Satadel Chatterjee, Jin He, Malcolm E. Kenney, Hedy E. Larkin, Hasan Mukhter, Boris D. Rihter, and Syed I. A. Zaidi "Signal transduction and metabolic changes during tumor cell apoptosis following phthalocyanine-sensitized photodynamic therapy", Proc. SPIE 1881, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy II, (18 June 1993); https://doi.org/10.1117/12.146317

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