Combinations of Anticancer Ti(IV) Phenolato Complexes with Other Anticancer Drugs: Toxicity and Cytotoxicity Measurements in vitro and in vivo
2Department of Cell and Developmental Biology, Alexander Silberman Institute of Life Science, The Hebrew University of Jerusalem, Jerusalem
The significant drawbacks of cisplatin, namely its high toxicity and development of drug-resistance, initiated an extensive search for other metals that can lead to anti-cancer activity. Ti(IV) complexes showed promising cytotoxic activity, and two Ti(IV) based complexes reached clinical trials. Nevertheless, these complexes have failed the trials due to instability in aqueous environment. Our group designed a new family of anti-cancer Ti(IV) complexes based on phenolato ligands, which showed high cytotoxic activity toward numerous cancer cell lines and enhanced stability in aqueous environment.
Combination therapy is very common in clinical treatment of cancer. By combining two drugs or more, the doses required to reach the desired effect are reduced, and consequently, side effects, toxicity, and the risk of developing drug resistance are reduced as well.
In earlier research, cytotoxicity measurements of the combinations of phenolato Ti(IV) complexes with other organic and inorganic anticancer drugs were performed on different types of cancer cell lines. The combinations showed mostly synergistic and additive behavior, which is medicinally valuable.1
Herein, specific combinations of phenolato Ti(IV) complexes with the drug commonly employed for a tested cell line are presented. The cell lines that respond best to the Ti(IV) phenolato complexes were identified by the NIH screening test. In vitro and in vivo anticancer measurements of the combination of the phenolato Ti(IV) complex with the drug that is clinically used to treat the identified cancer type were performed. Achievements in these directions will be discussed.
(1) Ganot, N.; Redko, B.; Gellerman, G.; Tshuva, E. Y. Rsc Adv. 2015, 5 (11), 7874–7879.
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