Small-molecule anthracene-induced cytotoxicity and induction of apoptosis through generation of reactive oxygen species

Rong Fu Chen, Chung Long Chou, Ming Ren Wang, Chieh Fu Chen, Jyh Fei Liao, Li Kang Ho, Chi Wei Tao, Hsu Shan Huang

研究成果: 雜誌貢獻文章同行評審

4 引文 斯高帕斯(Scopus)

摘要

A series of anthracene derivatives have been synthesized, and their potential individual cytotoxicity was evaluated using Jurkat T cells and peripheral blood mononuclear cells (PBMCs) in vitro. These compounds, except for 2l, showed less cytotoxicity in PBMCs than mitoxantrone. We also analyzed the antiproliferative activity of these derivatives using the annexin V/propidium iodide assay. These synthetic compounds induced apoptosis, thus leading to antitumor effects. Compounds 2b, 2e, 2f, 2g, 2h, 2i, 2j, and mitoxantrone produced dose-dependent cytotoxicity, while the antiproliferative activity of the anthracene pharmacophore was retained in Jurkat T cells base on the detection of DNA degradation and membrane unpacking. These clearly indicate a correlation between cytotoxicity and antitumor activity. Unlike mitoxantrone, cytotoxic properties were observed, as documented by the reactivity of these novel compounds against Jurkat T cells and PBMCs as normal cells, respectively. Various concentrations of 2b, 2e, 2f, 2g, 2h, 2i, and 2j preparations also inhibited Jurkat T cell proliferation and induced apoptosis of Jurkat T cells, potentially confirmed through the detection of DNA degradation and membrane unpacking. In the present report we also investigated the antiinflammatory activity against phorbol-12-myristate-13-acetate induced superoxide anion production, a marker for an inflammatory mediator produced by neutrophils, with IC50 (μM) values of 2b, 2h, 2l, and 2o of 4.28±0.89, 3.31±0.88, 4.38±0.25, and 5.45±1.78, respectively. These results suggest that, in addition to the specific chromosomal aberrations and cell death, elevated apoptosis could also be a marker for exposure to anthracene derivatives.
原文英語
頁(從 - 到)838-845
頁數8
期刊Biological and Pharmaceutical Bulletin
27
發行號6
DOIs
出版狀態已發佈 - 六月 2004
對外發佈Yes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology, Toxicology and Pharmaceutics(all)

指紋 深入研究「Small-molecule anthracene-induced cytotoxicity and induction of apoptosis through generation of reactive oxygen species」主題。共同形成了獨特的指紋。

引用此