In Vivo Anticancer Activity of a Nontoxic Inert Phenolato Titanium Complex: High Efficacy on Solid Tumors Alone and Combined with Platinum Drugs

Nitzan Ganot, Ori Briaitbard, Asaad Gammal, Joseph Tam*, Jacob Hochman, Edit Y. Tshuva

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Due to the toxicity of platinum compounds used in the clinic as anticancer chemotherapies, titanium serves as a safe and attractive alternative. Lately, we introduced a new family of Ti complexes based on readily available phenolato ligands, demonstrating incredibly high hydrolytic stability, with the lead compound phenolaTi demonstrating wide cytotoxic activity toward the NCI-60 panel of human cancer cell lines, with an average GI50 value of 4.7±2 μm. Herein, we evaluated in vivo: a) the safety, and b) the growth inhibitory capacity (efficacy) of this compound. PhenolaTi was found to be effective in vivo against colon (CT-26) and lung (LLC-1) murine cell lines in syngeneic hosts and toward a human colon cancer (HT-29) cell line in immune-deficient (Nude) mice, with an efficacy similar to that of known chemotherapy. Notably, no clinical signs of toxicity were observed in the treated mice, namely, no effect on body weight, spleen weight or kidney function, unlike the effects observed with the positive control Pt drugs. Studies of combinations of phenolaTi and Pt drugs provided evidence that similar efficacy with decreased toxicity may be achieved, which is highly valuable for medicinal applications.

Original languageAmerican English
Pages (from-to)2290-2296
Number of pages7
JournalChemMedChem
Volume13
Issue number21
DOIs
StatePublished - 6 Nov 2018

Bibliographical note

Funding Information:
We thank Liraz Larush and Prof. Shlomo Magdassi for the development of nano-formulations. Funding was received from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreements 779689 and 676841 to E.Y.T. and J.T., respectively).

Publisher Copyright:
© 2018 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Keywords

  • cisplatin
  • drug combinations
  • metallodrugs
  • nephrotoxicity
  • titanium

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