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

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 4.6μM 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 4h 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. Organogallium(III) complexes containing carboxylato or heterocyclic thiolato ligands have been tested for the in vitro antitumoral activity against HNSCC. [Display omitted]