Organogallium(III) complexes as apoptosis promoting anticancer agents for head and neck squamous cell carcinoma (HNSCC) cell lines

被引:20
作者
Kaluderovic, Milena R. [2 ]
Kaluderovic, Goran N. [1 ,3 ]
Gomez-Ruiz, Santiago [4 ]
Paschke, Reinhard [1 ]
Hemprich, Alexander [2 ]
Kuehling, Jan [5 ]
Remmerbach, Torsten W. [2 ,6 ]
机构
[1] Univ Halle Wittenberg, Biozentrum, D-06120 Halle, Germany
[2] Univ Leipzig, Dept Oral Maxillofacial & Facial Plast Surg, D-04103 Leipzig, Germany
[3] Univ Halle Wittenberg, Inst Chem, D-06120 Halle, Germany
[4] Univ Rey Juan Carlos, Dept Quim Inorgan & Analit, ESCET, Madrid 28933, Spain
[5] Max Planck Res Unit Enzymol Prot Folding, D-06120 Halle, Germany
[6] Griffith Univ, Griffith Hlth Inst, Griffith, Qld 4222, Australia
关键词
Anticancer drugs; Cytotoxicity; Apoptosis; Caspase activity; Cell cycle; Gallium(III) complexes; GALLIUM(III) COMPLEXES; METAL-COMPLEXES; CANCER-CELLS; CISPLATIN; MECHANISMS; DRUGS; DERIVATIVES; INHIBITION; TITANOCENE; EXPRESSION;
D O I
10.1016/j.jinorgbio.2010.10.013
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Organogallium(III) dinuclear (1-9) and tetranuclear (10) complexes present potential therapeutic agents for the treatment of various types of cancer. The antiproliferative activity of 1-10 was evaluated with cell lines of head and neck squamous cell carcinomas, e.g. HN (soft palate), Cal27, Cal33 (tongue) and FaDu (hypopharynx) cell lines. The activity of compound 8 is comparable with that of cisplatin on cell line Cal27 (IC50 4.6 mu M for both compounds). The mode of cell death induced, caspase activity and cell cycle analysis were evaluated for potential hit compounds 3, 5 and 8 Potential hit compounds 3, 5 and 8 were further evaluated for the mode of cell death, caspase activity and cell cycle analysis. Apoptosis induced by compounds 3,5 and 8 on Cal27 and FaDu cells was confirmed by DNA laddering, as well as acridine orange (AO) and ethidium bromide (EB) double staining. These compounds (3,5 and 8) induced caspase-independent apoptosis (within 4 h of action) in cell line Cal27. Extrinsic-mediated apoptosis associated with caspase 8 and 3 activation is the main mode of cytotoxicity induced on FaDu cells by compounds 3, 5 and 8. Cell cycle perturbations caused by these compounds are also observed. Our data suggest that compounds 3, 5 and 8 should be studied further for the treatment of head and neck cancer. (C) 2010 Elsevier Inc. All rights reserved.
引用
收藏
页码:164 / 170
页数:7
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