Anticancer Activity of Polyoxometalate-Bisphosphonate Complexes: Synthesis, Characterization, in Vitro and in Vivo Results

Amandine Boulmier, Xinxin Feng, Olivier Oms, Pierre Mialane, Eric Rivière, Christopher J. Shin, Jiaqi Yao, Tadahiko Kubo, Taisuke Furuta, Eric Oldfield, Anne Dolbecq

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Abstract

We synthesized a series of polyoxometalate-bisphosphonate complexes containing MoVIO6 octahedra, zoledronate, or an N-alkyl (n-C6 or n-C8) zoledronate analogue, and in two cases, Mn as a heterometal. Mo6L2 (L = Zol, ZolC6, ZolC8) and Mo4L2Mn (L = Zol, ZolC8) were characterized by using single-crystal X-ray crystallography and/or IR spectroscopy, elemental and energy dispersive X-ray analysis and 31P NMR. We found promising activity against human nonsmall cell lung cancer (NCI-H460) cells with IC50 values for growth inhibition of ∼5 μM per bisphosphonate ligand. The effects of bisphosphonate complexation on IC50 decreased with increasing bisphosphonate chain length: C0 ≈ 6.1×, C6 ≈ 3.4×, and C8 ≈ 1.1×. We then determined the activity of one of the most potent compounds in the series, Mo4Zol2Mn(III), against SK-ES-1 sarcoma cells in a mouse xenograft system finding a ∼5× decrease in tumor volume than found with the parent compound zoledronate at the same compound dosing (5 μg/mouse). Overall, the results are of interest since we show for the first time that heteropolyoxomolybdate-bisphosphonate hybrids kill tumor cells in vitro and significantly decrease tumor growth, in vivo, opening up new possibilities for targeting both Ras as well as epidermal growth factor receptor driven cancers.

Original languageEnglish (US)
Pages (from-to)7558-7565
Number of pages8
JournalInorganic Chemistry
Volume56
Issue number13
DOIs
StatePublished - Jul 3 2017

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ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Inorganic Chemistry

Cite this

Boulmier, A., Feng, X., Oms, O., Mialane, P., Rivière, E., Shin, C. J., Yao, J., Kubo, T., Furuta, T., Oldfield, E., & Dolbecq, A. (2017). Anticancer Activity of Polyoxometalate-Bisphosphonate Complexes: Synthesis, Characterization, in Vitro and in Vivo Results. Inorganic Chemistry, 56(13), 7558-7565. https://doi.org/10.1021/acs.inorgchem.7b01114