Caspase-independent apoptosis, in human MCF-7c3 breast cancer cells, following photodynamic therapy, with a novel water-soluble phthalocyanine.
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.
Vittar
Natalia B Rumie
NB
Departamento Biología Molecular, Facultad de Ciencias Exactas, Universidad Nacional de Río Cuarto, Ruta 8 Km 601, Río Cuarto, Argentina.
Awruch
Josefina
J
Azizuddin
Kashif
K
Rivarola
Viviana
V
D017209:Apoptosis / Q000187:drug effects*; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology*; D002154:Calpain / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002843:Chromatin / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004273:DNA, Neoplasm / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000494:pharmacology* / Q000627:therapeutic use*; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D008933:Mitochondrial Swelling / Q000187:drug effects; D009942:Organometallic Compounds / Q000494:pharmacology* / Q000627:therapeutic use*; D010718:Phosphatidylserines / Q000378:metabolism; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology / Q000627:therapeutic use; D021381:Protein Transport / Q000187:drug effects; D012995:Solubility / Q000187:drug effects; D014867:Water / Q000737:chemistry*
D051033:Apoptosis Inducing Factor; D051023:BH3 Interacting Domain Death Agonist Protein; D002843:Chromatin; D004273:DNA, Neoplasm; D007211:Indoles; D009942:Organometallic Compounds; D010718:Phosphatidylserines; D017319:Photosensitizing Agents; C549929:ZnPc(COOH)16; D014867:Water; D002154:Calpain; D020169:Caspases