Phthalocyanine-mediated photodynamic therapy induces cell death and a G0/G1 cell cycle arrest in cervical cancer cells.
We have developed a series of novel photosensitizers which have potential for anticancer photodynamic therapy (PDT). Photosensitizers include zinc phthalocyanine tetra-sulphonic acid and a family of derivatives with amino acid substituents of varying alkyl chain length and degree of branching. Subcellular localization of these photosensitizers at the phototoxic IC(50) concentration in human cervical carcinoma cells (SiHa Cells) was similar to that of the lysosomal dye Lucifer Yellow. Subsequent nuclear relocalization was observed following irradiation with 665nm laser light. The PDT response was characterized using the Sulforhodamine B cytotoxicity assay. Flow cytometry was used for both DNA cell cycle and dual Annexin V-FITC/propidium iodide analysis. Phototoxicity of the derivatives was of the same order of magnitude as for tetrasulphonated phthalocyanine but with an overall trend of increased phototoxicity with increasing amino acid chain length. Our results demonstrate cell death, inhibition of cell growth, and G(0)/G(1) cell cycle arrest during the phthalocyanine PDT-mediated response.
Haywood-Small
S L
SL
Centre for Photobiology and Photodynamic Therapy, School of Biochemistry and Microbiology, University of Leeds, Leeds LS2 9JT, UK. s.l.hankin@sheffield.ac.uk
Vernon
D I
DI
Griffiths
J
J
Schofield
J
J
Brown
S B
SB
D002453:Cell Cycle / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D005260:Female; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D020128:Inhibitory Concentration 50; D054833:Isoindoles; D015394:Molecular Structure; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D002583:Uterine Cervical Neoplasms / Q000473:pathology*
D007211:Indoles; D054833:Isoindoles; D017319:Photosensitizing Agents; C013647:phthalocyanine