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A Copper Complex, ghn‐12, as a sensitization of DNA to UVA offers potential for a novel photochemotherapy
Author(s) -
Lai Feng-Jie,
Liang Cheng-Hsuan,
Cheng Ching-Li,
Lin Rrong-Kai,
Chang Nan-Shan,
Lin Chu-Chieh
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.999.5
Subject(s) - apoptosis , propidium iodide , cell cycle , cytotoxicity , chemistry , flow cytometry , annexin , programmed cell death , cancer research , microbiology and biotechnology , cell , biology , biochemistry , in vitro
Photochemotherapy is a modern therapy modality, based upon the application of a photosensitizing agent onto the tissue followed by illumination with light sources, which is a proven therapeutic strategy for a number of non‐malignant hyperproliferative skin diseases and various cancers. The aim of the present study is to investigate a new synthesis copper complex (ghn‐12, Chemical Formula: C53H39ClCuN8O5) as a potent photocytotoxic agent. Photoinduced DNA cleavage activity, cell cytotoxicity, cell cycle distribution and apoptosis assay are used to investigate the effect of ghn‐12 on therapeutic applications. Ghn‐12 induced supercoiled pUC19 DNA cleavage from supercoiled to nicked circular form at a low‐power monochromatic UV‐A light of 365 nm. Flow cytometry analysis revealed that photoinduced ghn‐12 sensitized squamous cell carcinoma (SCC15) cells to arrest in the G0/G1 and S‐G2/M phases of the cell cycle with a concomitantly significant increase in the sub‐G1 cell population, indicating cell death by apoptosis. This photoinduced apoptosis process was accompanied by activation of caspase‐3 expression and FITC Annexin V staining after SCC15 cells treated with ghn‐12. Our data suggest that a new photosensitizing compound, ghn‐12, exhibiting light‐induced cleavage of double‐stranded DNA and causing apoptosis of squamous cell carcinoma. Ghn‐12 is a potential therapeutic reagent. Research support by grant from the National Science Council, Taiwan Grant NSC99‐2314‐B‐384 ‐002 ‐MY3.