In vitro combinations of inert phenolato Ti(iv) complexes with clinically employed anticancer chemotherapy: synergy with oxaliplatin on colon cells

Advanced anticancer phenolato titanium(iv) complexes were combined with known chemotherapeutic anticancer drugs applied in the clinic and were analyzed in vitro on cell lines most sensitive to the Ti(iv) complex and relevant to the clinical application of the known drugs. Combination of the Ti(iv) complex with cisplatin on ovarian cells showed mostly an additive behavior, also on a line resistant to cisplatin. Combination of the Ti(iv) complex with fluorouracil on colon cells gave near additive behavior, and that with oxaliplatin gave a synergistic behavior at a wide range of Ti : Pt ratios, but only when the drugs were administered together. Increasing the time intervals between the administration of Ti and of Pt turned the behavior to antagonistic, suggesting some deactivation of Pt by the Ti agent. For combinations where the drugs were applied together, the behavior depended on the effect level, and higher effects gave greater synergism, implying that technical aspects such as solubility are influential. Nevertheless, more complex patterns recorded for combinations where the drugs had been applied separately suggested multiple mechanisms with different concentration dependence. Overall the results point to high medicinal potential for the tested compounds for anticancer combination treatments.