Photodynamic effects of isosteric water-soluble phthalocyanines on human nasopharynx KB carcinoma cells

• Published in: European journal of medicinal chemistry Vol. 45; no. 9; pp. 4129 - 4139
• Main Authors: Marino, Julieta, García Vior, María C., Dicelio, Lelia E., Roguin, Leonor P., Awruch, Josefina
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Masson SAS 01.09.2010; Elsevier
• Subjects: Apoptosis; Apoptosis - drug effects; Apoptosis - radiation effects; Biological and medical sciences; Biological Transport; Cell Proliferation - drug effects; Cell Proliferation - radiation effects; Humans; Indoles - chemistry; Indoles - metabolism; Indoles - pharmacology; Intracellular Space - metabolism; KB Cells; Lysosomes; Medical sciences; Nasopharyngeal Neoplasms - pathology; Photochemical Processes; Photochemotherapy; Photodynamic therapy; Photoradiation therapy and photosensitizing agent; Phthalocyanines; Singlet oxygen; Solubility; Treatment with physical agents; Treatment. General aspects; Tumors; Water - chemistry; Lysosomes; KB cells; Photodynamic therapy; Singlet oxygen; Phthalocyanines; Apoptosis; Divalent metal Complexes; Carcinoma; Organic cation; Zinc II Complexes; Lysosome; Cytotoxicity; Nasopharynx; Organic sulfide; Chemical synthesis; Tumor cell; Human; Singlet state; Malignant tumor; In vitro; Biological activity; Quaternary ammonium compound; Water soluble compound; Cell line; Metallophthalocyanine; KB cell line; Phototoxicity; Cancer
• DOI: 10.1016/j.ejmech.2010.06.002
• ISSN: 0223-5234

The photodynamic activity of water-soluble cationic zinc(II) phthalocyanines using human nasopharynx carcinoma (KB cells) was investigated. A sulfur-linked cationic dye, named: 2,9(10),16(17),23(24)-tetrakis[(2-trimethylammonium)ethylsulfanyl]phthalocyaninatozinc(II) tetraioidide ( 13) is the most active of four sensitizer assays and shows a singlet oxygen quantum yield of 0.58 and a higher bathochromic shift of 10 nm for the Q-band as compared with the oxygen-linked cationic aliphatic phthalocyanine: 2,9(10),16(17),23(24)-tetrakis[(2-trimethylammonium)ethoxy]phthalocyaninatozinc(II) tetraioidide ( 11) and the best photo-stability in water in comparison with their tetra-α-substituted counterparts 1,8(11),15(18),22(25)-tetrakis[(2-trimethylammonium)ethoxy]phthalocyaninatozinc(II) tetraioidide ( 12) and 1,8(11),15(18),22(25)-tetrakis[(2-trimethylammonium)ethylsulfanyl]phthalocyaninatozinc(II) tetraioidide ( 14). Phthalocyanine 13, partially localized in lysosomes, led to cell photoinactivation in a concentration- and light dose-dependent manner. After photodynamic treatment, compound 13 induced an apoptotic response – as indicated by morphological cell changes – an increase in the activity of caspase-3 and the cleavage of poly-ADP-ribose-polymerase substrate (PARP). β-Sulfur-linked cationic aliphatic phthalocyanine 13 shows a Φ Δ = 0.58 and λ max = 686 nm, no dark cytotoxicity and triggers lysosomal-induced apoptosis after irradiation leading to 90% cell death. [Display omitted]