Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Ganot N

PROVIDER: S-EPMC6003540 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Ganot N N Tshuva E Y EY

RSC advances 20180206 11

Advanced anticancer phenolato titanium(iv) complexes were combined with known chemotherapeutic anticancer drugs applied in the clinic and were analyzed <i>in vitro</i> 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 ad ...[more]

PMID: 30009018

Similar Datasets

Project description:The recent X-ray structure of titanium(IV)-bound human serum transferrin (STf) exhibiting citrate as a synergistic anion reveals a difference in Ti(IV) coordination versus iron(III), the metal endogenously delivered by the protein to cells. This finding enriches our bioinspired drug design strategy for Ti(IV)-based anticancer therapeutics, which applies a family of Fe(III) chelators termed chemical transferrin mimetic (cTfm) ligands to inhibit Fe bioavailability in cancer cells. Deferasirox, a drug used for iron overload disease, is a cTfm ligand that models STf coordination to Fe(III), favoring Fe(III) binding versus Ti(IV). This metal affinity preference drives deferasirox to facilitate the release of cytotoxic Ti(IV) intracellularly in exchange for Fe(III). An aqueous speciation study performed by potentiometric titration from pH 4 to 8 with micromolar levels of Ti(IV) deferasirox at a 1:2 ratio reveals exclusively Ti(deferasirox)2 in solution. The predominant complex at pH 7.4, [Ti(deferasirox)2]2-, exhibits the one of the highest aqueous stabilities observed for a potent cytotoxic Ti(IV) species, demonstrating little dissociation even after 1 month in cell culture media. UV-vis and 1H NMR studies show that the stability is unaffected by the presence of biomolecular Ti(IV) binders such as citrate, STf, and albumin, which have been shown to induce dissociation or regulate cellular uptake and can alter the activity of other antiproliferative Ti(IV) complexes. Kinetic studies on [Ti(deferasirox)2]2- transmetalation with Fe(III) show that a labile Fe(III) source is required to induce this process. The initial step of this process occurs on the time scale of minutes, and equilibrium for the complete transmetalation is reached on a time scale of hours to a day. This work reveals a mechanism to deliver Ti(IV) compounds into cells and trigger Ti(IV) release by a labile Fe(III) species. Cellular studies including other cTfm ligands confirm the Fe(III) depletion mechanism of these compounds and show their ability to induce early and late apoptosis.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets