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The Bulk Osteosarcoma and Osteosarcoma Stem Cell Activity of a Necroptosis‐Inducing Nickel(II)–Phenanthroline Complex
Author(s) -
Eskandari Arvin,
Flamme Marie,
Xiao Zhiyin,
Suntharalingam Kogularamanan
Publication year - 2020
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.202000231
Subject(s) - necroptosis , osteosarcoma , propidium iodide , cisplatin , programmed cell death , chemistry , cancer research , apoptosis , poly adp ribose polymerase , microbiology and biotechnology , biology , biochemistry , medicine , polymerase , enzyme , chemotherapy
We report the anti‐osteosarcoma and anti‐osteosarcoma stem cell (OSC) properties of a nickel(II) complex, 1 . 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 elevating intracellular reactive oxygen species (ROS) or hyperactivation of poly ADP ribose polymerase (PARP‐1). ROS elevation and PARP‐1 activity are traits that have been observed for established necroptosis inducers such as shikonin, TRAIL and glutamate. Thus the necroptosis pathway evoked by 1 is distinct. To the best of our knowledge, this is the first report into the anti‐osteosarcoma and anti‐OSC properties of a nickel complex.