Gallium(<scp>iii</scp>)-polypyridyl complexes as anti-osteosarcoma stem cell agents

Robin, Perrine; Singh, Kuldip; Suntharalingam, Kogularamanan

doi:10.1039/c9cc08962d

Cited by 18 publications

(54 citation statements)

References 28 publications

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“…The addition of 1 (IC 20 values for 10 days) to individual cell suspensions of U2OS‐MTX cells noticeably decreased the size of sarcospheres formed (Figure ). Under the same conditions, cisplatin, carboplatin, or salinomycin (IC 20 values for 10 days) was shown here, and previously, to have no major effect on the size of sarcospheres formed (Figure ) . To determine the effect of 1 on sarcosphere viability, the resazurin‐based indicator, TOX8 was employed.…”

Section: Resultssupporting

confidence: 69%

“…The tyrosine kinase protein, CD117 is overexpressed on the cell surface of OSCs . Using a previously reported method, we isolated OSC‐enriched, CD117‐positive cells by treating U2OS cells with methotrexate (300 nM) for 4 days . This method allowed us to generate OSC‐rich populations of U2OS cells, which we henceforth denote as U2OS‐MTX cells.…”

Section: Resultsmentioning

confidence: 99%

“…The cells (labelled U2OS‐MTX cells) were used immediately. U2OS‐MTX cells were characterised according to CD117 expression using flow cytometry as previously reported …”

Section: Methodsmentioning

confidence: 99%

“…Breast and glioma CSC‐potent compounds containing metals have been recently developed by us and others . We recently reported a series of gallium(III) complexes containing polypyridyl ligands with micromolar to nanomolar potency towards bulk osteosarcoma cells and OSCs (in monolayer and 3D cell culture systems) . Mechanistic studies showed that the most effective gallium(III) complex in the series killed osteosarcoma cells, most probably, by inducing genomic DNA damage …”

Section: Introductionmentioning

confidence: 99%

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The Bulk Osteosarcoma and Osteosarcoma Stem Cell Activity of a Necroptosis‐Inducing Nickel(II)–Phenanthroline Complex

Eskandari

Flamme²,

Xiao

et al. 2020

ChemBioChem

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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 threedimensional 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 depolarisa-tion 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.

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Section: Resultssupporting

confidence: 69%

Section: Resultsmentioning

confidence: 99%

“…The cells (labelled U2OS‐MTX cells) were used immediately. U2OS‐MTX cells were characterised according to CD117 expression using flow cytometry as previously reported …”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Bulk Osteosarcoma and Osteosarcoma Stem Cell Activity of a Necroptosis‐Inducing Nickel(II)–Phenanthroline Complex

Eskandari

Flamme²,

Xiao

et al. 2020

ChemBioChem

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“…Since the introductiono fp latinum-based chemotherapeutics for the treatment of cancer, [1] there has been sustained effort toward discovering new anticancer metallodrugs of even greater efficacy and selectivity.Awide range of elements have formed the basis of these investigations,h ighlighted by recent examples of complexes based on Fe II , [2] Ga III , [3] Ag I , [4] Re I , [5] Os II , [6] Ir III [7,8] and Au I . [9] Ru II -based compounds have perhaps been the subjecto ft he mosti ntense focus, with the early compounds NAMI-A [10] and KP1019 [11] then the promising RAPTA [12] and RAED [13] familieso fc ompounds pavingt he way for continued research in this area.…”

Section: Introductionmentioning

confidence: 99%

Homo‐ and Hetero‐dinuclear Arene‐Linked Osmium(II) and Ruthenium(II) Organometallics: Probing the Impact of Metal Variation on Reactivity and Biological Activity

Wilson

Prior

Sandland

et al. 2020

Chemistry A European J

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Dinuclear metallodrugs offer much potential in the development of novel anticancer chemotherapeutics as a result of the distinct interactions possible with bio‐macromolecular targets and the unique biological activity that can result. Herein, we describe the development of isostructural homo‐dinuclear OsII–OsII and hetero‐dinuclear OsII–RuII organometallic complexes formed from linking the arene ligands of [M(η6‐arene)(C2O4)(PTA)] units (M=Os/Ru; PTA=1,3,5‐triaza‐7‐phosphaadamantane). Using these complexes together with the known RuII–RuII analogue, a chromatin‐modifying agent, we probed the impact of varying the metal ions on the structure, reactivity and biological activity of these complexes. The complexes were structurally characterised by X‐ray diffraction experiments, their stability and reactivity were examined by using 1H and 31P NMR spectroscopy, and their biological activity was assessed, alongside that of mononuclear analogues, through MTT assays and cell‐cycle analysis (HT‐29 cell line). The results revealed high antiproliferative activity in each case, with cell‐cycle profiles of the dinuclear complexes found to be similar to that for untreated cells, and similar but distinct profiles for the mononuclear complexes. These results indicate these complexes impact on cell viability predominantly through a non‐DNA‐damaging mechanism of action. The new OsII–OsII and OsII–RuII complexes reported here are further examples of a family of compounds operating via mechanisms of action atypical of the majority of metallodrugs, and which have potential as tools in chromatin research.

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The Osteosarcoma Stem Cell Activity of a Gallium(III)‐Phenanthroline Complex Appended to Salicylate

et al. 2022

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We report the synthesis, characterisation, and anti‐osteosarcoma properties of a gallium(III) complex (1) comprising of two 1,10‐phenanthroline ligands and salicylate, a non‐steroidal anti‐inflammatory drug. The gallium(III) complex 1 displays micromolar potency towards bulk osteosarcoma cells and osteosarcoma stem cells (OSCs). Notably, the gallium(III) complex 1 exhibits significantly higher toxicity towards OSCs grown in monolayer and three‐dimensional cultures than cisplatin, a frontline anti‐osteosarcoma drug. Nuclei isolation and immunoblotting studies show that the gallium(III) complex 1 enters osteosarcoma cell nuclei and induces DNA damage. Flow cytometry and cytotoxicity studies (in the presence of prostaglandin E2) indicate that the gallium(III) complex 1 downregulates cyclooxygenase‐2 (COX‐2) expression and kills osteosarcoma cells in a COX‐2‐dependent manner. Further, the mode of osteosarcoma cell death evoked by the gallium(III) complex 1 is characterised as caspase‐dependent apoptosis.

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Gallium(iii)-polypyridyl complexes as anti-osteosarcoma stem cell agents

Abstract: Gallium(iii) complexes with polypridyl ligands are shown to kill bulk osteosarcoma cells and osteosarcoma stem cells (OSCs) with up to nanomolar potency.

Cited by 18 publications

References 28 publications

The Bulk Osteosarcoma and Osteosarcoma Stem Cell Activity of a Necroptosis‐Inducing Nickel(II)–Phenanthroline Complex

The Bulk Osteosarcoma and Osteosarcoma Stem Cell Activity of a Necroptosis‐Inducing Nickel(II)–Phenanthroline Complex

Homo‐ and Hetero‐dinuclear Arene‐Linked Osmium(II) and Ruthenium(II) Organometallics: Probing the Impact of Metal Variation on Reactivity and Biological Activity

The Osteosarcoma Stem Cell Activity of a Gallium(III)‐Phenanthroline Complex Appended to Salicylate

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