Organogallium(III) complexes as apoptosis promoting anticancer agents for head and neck squamous cell carcinoma (HNSCC) cell lines |
| |
Authors: | Kaluđerović Milena R Kaluđerović Goran N Gómez-Ruiz Santiago Paschke Reinhard Hemprich Alexander Kühling Jan Remmerbach Torsten W |
| |
Institution: | a Department of Oral, Maxillofacial and Facial Plastic Surgery, University of Leipzig, Nürnberger Str. 57, D-04103 Leipzig, Germanyb Biozentrum, Martin-Luther-Universität Halle-Wittenberg, Weinbergweg 22, 06120 Halle, Germanyc Institut für Chemie, Martin-Luther-Universität Halle-Wittenberg, Kurt-Mothes-Straße 2, 06120 Halle, Germanyd Departamento de Química Inorgánica y Analítica, E.S.C.E.T., Universidad Rey Juan Carlos, 28933 Móstoles, Madrid, Spaine Max Planck Research Unit for Enzymology of Protein Folding, Weinbergweg 22, 06120 Halle, Germanyf Griffith Health Institute, Griffith University, Gold Coast campus, 4222 Queensland, Australia |
| |
Abstract: | 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 μM 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. |
| |
Keywords: | Anticancer drugs Cytotoxicity Apoptosis Caspase activity Cell cycle Gallium(III) complexes |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|