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The bulk osteosarcoma and osteosarcoma stem cell activity of a necroptosis-inducing nickel(II)-phenanthroline complex.

journal contribution
posted on 2020-05-22, 10:32 authored by Arvin Eskandari, Marie Flamme, Zhiyin Xiao, Kogularamanan Suntharalingam
We report the anti-osteosarcoma and anti-osteosarcoma stem cell (OSC) properties of a nickel(II) complex, 1. The nickel(II) complex, 1 displays similar potency towards bulk osteosarcoma cells and OSCs, in the micromolar range. Notably, 1 displays similar or better OSC potency than the clinically approved platinum(II) anticancer drugs, cisplatin and carboplatin, in two- and three-dimensional osteosarcoma cell cultures. Mechanistic studies revealed that 1 induces osteosarcoma cell death by necroptosis, an ordered form of necrosis. The nickel(II) complex, 1 triggers necrosome-dependent mitrochondrial membrane depolarisation and propidium iodide uptake. Interestingly, 1 does not evoke necroptosis by intracellular reactive oxygen species (ROS) elevation or poly ADP ribose polymerase (PARP-1) hyperactivation. ROS elevation and PARP-1 activity are traits that have been observed for established necroptosis-inducers such as shikinon, TRAIL, and glutamate. Thus the necroptosis pathway evoked by 1 is distinct. To the best of our awareness this is the first report into the anti-osteosarcoma and anti-OSC properties of a nickel complex.

Funding

K.S. is supported by an EPSRC New Investigator Award (EP/S005544/1)

History

Citation

Eskandari, A., Flamme, M., Xiao, Z. and Suntharalingam, K. (2020), The bulk osteosarcoma and osteosarcoma stem cell activity of a necroptosis‐inducing nickel(II)‐phenanthroline complex. ChemBioChem. Accepted Author Manuscript. doi:10.1002/cbic.202000231

Version

  • AM (Accepted Manuscript)

Published in

Chembiochem

Publisher

Wiley

issn

1439-4227

eissn

1439-7633

Acceptance date

2020-05-16

Copyright date

2020

Language

eng

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