Caspase-independent apoptosis,in human MCF-7c3 breast cancer cells,following photodynamic therapy,with a novel water-soluble phthalocyanine |
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| Authors: | Natalia B. Rumie Vittar Josefina Awruch Kashif Azizuddin Viviana Rivarola |
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| Affiliation: | 1. Facultad de Ciencias Básicas, Escuela de Ciencias Químicas, Universidad Pedagógica y Tecnológica de Colombia-UPTC, Colombia;2. Department of Chemistry and Centre for Catalysis Research and Innovation, University of Ottawa, 10 Marie Curie, Ottawa, K1N 6N5, Canada;3. Division of Cardiac Surgery Research, Bio-Nanomaterials Chemistry and Engineering Laboratory, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, Ontario, K1Y 4W7, Canada;4. Departamento de ciencias del ambiente, Facultad de Química y Biología, Universidad de Santiago de Chile, (USACH), Santiago, Chile;5. Departamento de Química Física, Facultad de Química, Pontificia Universidad Católica de Chile, Santiago, Chile;6. Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada;1. Karadeniz Technical University, Faculty of Pharmacy, Department of Biochemistry, Trabzon, Turkey;2. Karadeniz Technical University, Faculty of Science, Department of Chemistry, Trabzon, Turkey |
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| Abstract: | A new water-soluble phthalocyanine derivative, 2,3,9,10,16,17,23,24-octakis(3-aminopropyloxy) phthalocyaninato zinc II (PoII) was studied as a photosensitizer for photodynamic therapy (PDT) in MCF-7c3 cells. We report here that PoII and red light induces apoptosis. However, the precise mechanism appears to differ from that induced by PDT with other known phthalocyanines. The present study provides evidence that in the case of PoII, caspases do not participate in the apoptotic response. PoII-PDT-treated cells exhibited chromatin condensation and phosphatidylserine (PS) externalization. In the absence of light activation, PoII had no detectable cytotoxic effect. An early event upon PoII-PDT was photodamage to lysosomes, suggesting that they are the primary sites of action. Moreover, the treatment induces Bid activation, mitochondrial swelling and translocation of apoptosis-inducing factor (AIF) to the nucleus. An atypical proteolysis of poly(ADP-ribose) polymerase (PARP) indicative of calpain-like activation was observed. These data support the notion that an alternative mechanism of caspase-independent apoptosis was found in PoII-photosensitized cells. |
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