Titanates and Titanate-Auranofin Complexes for Potential Treatment of Cancer

Objectives: ”Monosodium titanates (MST) and amorphous peroxotitanates (APT) are inorganic ion-exchangers with affinity for specific metal ions, including Au (I), Au (III), Pd (II), and Hg (II). Titanates alone do not suppress fibroblast or monocyte metabolism, but deliver metal ions to these cells to suppress metabolism or alter cytokine secretion.  Auranofin (AF) is an ideal candidate for the treatment of cancer based on its ability to induce cellular apoptosis.  Our objective was to assess the effectiveness of using MST or APT as a local drug delivery system for AF suppressing the growth of human glioblastoma cells in vitro.“Methods: ” Human glioblastoma cells (MO59K) were exposed in vitro (n = 8 per condition) to titanates (0.1 - 100 µg/mL) alone or loaded with AF for 24, 48, and 72 h. Viable cell number was estimated by quantifying succinate dehydrogenase activity of the cultures post exposure (MTT method). Cell activities were normalized to cultures without titanates, then were compared with ANOVA and Tukey post-hoc analyses (α = 0.05). “Results: ” MST alone suppressed MO59K growth by 38, 23, and 22 % at 0.1 µg/mL for 24, 48 and 72 h respectively (significant p < 0.01). APT alone suppressed MO59K growth by 30, 46 and 47% at 10-50 µg/mL for 24, 48 and 72 h respectively.  However, MST loaded with AF suppressed MO59K growth by 45, 59, and 54%. APT loaded with AF suppressed MO59K growth by 50, 63, and 64% vs. control cultures, and all significantly greater than titanates alone (significant p < 0.01). “Conclusion: ” Titanates alone suppress the growth of human brain glioblastoma cell line; auranofin-loaded titanates significantly enhance growth suppression in vitro. These results suggest that auranofin-titanate complexes might be used as potent, local and robust drug delivery platforms for treatment of cancer.

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