title: Beta-carboline derivatives: novel photosensitizers that intercalate into DNA to cause direct DNA damage in photodynamic therapy.
abstract: Novel 1,3,9-trisubstituted beta-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 beta-carboline derivatives. Different from other clinical PDT drugs, beta-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.
authors.affiliation: State Key Laboratory of Biocontrol, Guangdong Key Laboratory of Therapeutic Functional Genes, Department of Biochemistry, College of Life Sciences, Sun Yat-sen (Zhongshan) University, 135 Xin Gang Xi Road, Guangzhou 510275, People's Republic of China.
authors.forename: Huaji
authors.initials: H
authors.lastname: Guan
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Liu
authors.forename: Wenlie
authors.initials: W
authors.lastname: Peng
authors.forename: Rihui
authors.initials: R
authors.lastname: Cao
authors.forename: Yan
authors.initials: Y
authors.lastname: Ma
authors.forename: Hongsheng
authors.initials: H
authors.lastname: Chen
authors.forename: Anlong
authors.initials: A
authors.lastname: Xu
mesh_terms: D000042:Absorption; D002243:Carbolines / Q000737:chemistry / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000187:drug effects* / Q000528:radiation effects; D004249:DNA Damage / Q000187:drug effects*; D015894:Genome, Human / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D007364:Intercalating Agents / Q000494:pharmacology*; D008027:Light; D008938:Mitosis / Q000187:drug effects; D009336:Necrosis / Q000532:radiotherapy; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*
chemical_list: D002243:Carbolines; D007364:Intercalating Agents; D017319:Photosensitizing Agents; D004247:DNA