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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:
 [1];  [1];  [1];  [1];  [1];  [1];  [2]
  1. 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 (China)
  2. 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 (China). E-mail: ls36@zsu.edu.cn
Publication Date:
OSTI Identifier:
20798899
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 342; Journal Issue: 3; Other Information: DOI: 10.1016/j.bbrc.2006.02.035; PII: S0006-291X(06)00326-3; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANTIOXIDANTS; APOPTOSIS; BIOSYNTHESIS; CELL PROLIFERATION; CLATHRATES; DNA; DNA DAMAGES; DRUGS; HELA CELLS; IRRADIATION; MITOSIS; NECROSIS; PHOTOCHEMICAL REACTIONS; THERAPY; TOXICITY; VITAMIN E

Citation Formats

Guan Huaji, Liu Xiaodong, Peng Wenlie, Cao Rihui, Ma Yan, Chen Hongsheng, and Xu Anlong. {beta}-carboline derivatives: Novel photosensitizers that intercalate into DNA to cause direct DNA damage in photodynamic therapy. United States: N. p., 2006. Web. doi:10.1016/j.bbrc.2006.02.035.
Guan Huaji, Liu Xiaodong, Peng Wenlie, Cao Rihui, Ma Yan, Chen Hongsheng, & Xu Anlong. {beta}-carboline derivatives: Novel photosensitizers that intercalate into DNA to cause direct DNA damage in photodynamic therapy. United States. doi:10.1016/j.bbrc.2006.02.035.
Guan Huaji, Liu Xiaodong, Peng Wenlie, Cao Rihui, Ma Yan, Chen Hongsheng, and Xu Anlong. Fri . "{beta}-carboline derivatives: Novel photosensitizers that intercalate into DNA to cause direct DNA damage in photodynamic therapy". United States. doi:10.1016/j.bbrc.2006.02.035.
@article{osti_20798899,
title = {{beta}-carboline derivatives: Novel photosensitizers that intercalate into DNA to cause direct DNA damage in photodynamic therapy},
author = {Guan Huaji and Liu Xiaodong and Peng Wenlie and Cao Rihui and Ma Yan and Chen Hongsheng and Xu Anlong},
abstractNote = {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.},
doi = {10.1016/j.bbrc.2006.02.035},
journal = {Biochemical and Biophysical Research Communications},
number = 3,
volume = 342,
place = {United States},
year = {Fri Apr 14 00:00:00 EDT 2006},
month = {Fri Apr 14 00:00:00 EDT 2006}
}