1. Substituted titanocenes induce caspase-dependent apoptosis in human epidermoid carcinoma cells in vitro and exhibit antitumour activity in vivo.
- Author
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Bannon JH, Fichtner I, O'Neill A, Pampillón C, Sweeney NJ, Strohfeldt K, Watson RW, Tacke M, and Mc Gee MM
- Subjects
- Animals, Blotting, Western, Body Weight drug effects, Carcinoma, Squamous Cell drug therapy, Carcinoma, Squamous Cell metabolism, Cell Cycle drug effects, Cell Proliferation drug effects, Female, HeLa Cells drug effects, Humans, Inhibitory Concentration 50, Mice, Mice, Nude, Organometallic Compounds chemistry, Titanium chemistry, Titanium pharmacology, Tumor Cells, Cultured drug effects, Antineoplastic Agents pharmacology, Apoptosis drug effects, Carcinoma, Squamous Cell pathology, Caspase 3 metabolism, Organometallic Compounds pharmacology
- Abstract
Titanocene compounds are a novel series of agents that exhibit cytotoxic effects in a variety of human cancer cells in vitro and in vivo. In this study, the antiproliferative activity of two titanocenes (Titanocenes X and Y) was evaluated in human epidermoid cancer cells in vitro. Titanocenes X and Y induce apoptotic cell death in epidermoid cancer cells, with IC50 values that are comparable to cisplatin. Characterisation of the cell death pathway induced by titanocene compounds in A431 cells revealed that apoptosis is preceded by cell cycle arrest and the inhibition of cell proliferation. The induction of apoptosis is dependent on the activation of caspase-3 and -7 but not caspase-8. Furthermore, the antitumour activity of Titanocene Y was tested in an A431 xenograft model of epidermoid cancer. Results indicate that Titanocene Y significantly reduced the growth of A431 xenografts with an antitumour effect similar to cisplatin. These results suggest that titanocenes represent a novel series of promising antitumour agents.
- Published
- 2007
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