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Issue 12, 2018
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Gallium(III)–2-benzoylpyridine-thiosemicarbazone complexes promote apoptosis through Ca2+ signaling and ROS-mediated mitochondrial pathways

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Abstract

Ga(III) compounds are highly promising candidates for antitumor therapy. The level of intracellular reactive oxygen species (ROS) is significantly increased after Ga(III) complex treatment, but these complexes are redox-inactive. To investigate the effects of Ga(III) complexes on ROS levels, we synthesized three bis-ligated gallium(III)–2-benzoylpyridine-thiosemicarbazone complexes and studied their antitumor mechanisms. The structures of the Ga(III) complexes were identified by X-ray single-crystal diffraction. Cytotoxicity analysis demonstrated that the ligands and gallium complexes exerted a higher antitumor activity and a lower cytotoxicity than those of normal cells. The most active complex was C3, which exhibited a better antitumor viability than its related ligands and the anticancer agent 3-AP. Thus, the Ga(III) complexes not only transmitted the iron ions but also induced intracellular Ca2+ release. As a result, the ROS standards in redox-active iron complexes were increased. The mechanism involved the release of Cyt C from the mitochondria which lack membrane potential, and then the activation of the caspase family proteins stimulated cell apoptosis.

Graphical abstract: Gallium(iii)–2-benzoylpyridine-thiosemicarbazone complexes promote apoptosis through Ca2+ signaling and ROS-mediated mitochondrial pathways

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Publication details

The article was received on 09 Feb 2018, accepted on 28 Apr 2018 and first published on 03 May 2018


Article type: Paper
DOI: 10.1039/C8NJ00697K
Citation: New J. Chem., 2018,42, 10226-10233
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    Gallium(III)–2-benzoylpyridine-thiosemicarbazone complexes promote apoptosis through Ca2+ signaling and ROS-mediated mitochondrial pathways

    J. Qi, K. Qian, L. Tian, Z. Cheng and Y. Wang, New J. Chem., 2018, 42, 10226
    DOI: 10.1039/C8NJ00697K

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