Beta-carboline derivatives: novel photosensitizers that intercalate into DNA to cause direct DNA damage in photodynamic therapy

Autor: Xiaodong Liu, Yan Ma, Hongsheng Chen, Huaji Guan, Anlong Xu, Wenlie Peng, Rihui Cao
Rok vydání: 2006
Předmět:
Zdroj: Biochemical and biophysical research communications. 342(3)
ISSN: 0006-291X
Popis: Novel 1,3,9-trisubstituted β-carboline derivatives were found to exhibit DNA photocleavage properties under visible light irradiation in a cell-free system, which could be reduced by antioxidant vitamin E. Their photo-cytotoxicity to human tumor cell line HeLa was confirmed, in which apoptosis only contributed a small part to the cell death, and necrosis was the dominating outcome of HeLa cells in photodynamic therapy (PDT) using β-carboline derivatives. Different from other clinical PDT drugs, β-carboline derivatives were demonstrated to be able to distribute in the nucleus and intercalate into DNA, and consequently cause direct DNA damage by photochemical reaction products in PDT, which was proved by the distinct DNA tails in the comet assay and the considerable amount of DNA damaged cells quantified by flow cytometry. This mechanism could be the explanation for the delay of cell proliferation at DNA synthesis and mitosis.
Databáze: OpenAIRE