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

Abstract

Ga(III) compounds are very promising candidates for antitumor therapy. Studies have shown that intracellular Reactive Oxygen Species (ROS) is significantly increased after Ga(III) complexes treatment, while these complexes are redox-inactive. To investigate how Ga(III) complexes affects the levels of ROS, we have synthesized three bis-liganded gallium(III)-2-benzoylpyridine-thiosemicarbazones complexes and studied antitumor mechanisms of these complexes. The structures of Ga(III) complexes were identified by X−ray single crystal diffraction. Cytotoxicity studies have shown that ligands and gallium complexes have higher antitumor activity and lower cytotoxicity than normal cells. The most active complex is C3, the antitumor viability of which is better than its related ligands and anticancer agent 3−AP. It shows that Ga(III) complexes not only transmit the iron ions, but also induce intracellular Ca2+ to release, and then the standards of ROS in redox-active iron complexes will be increased. Cyt C releases from mitochondria which is lack of membrane potential, then activated Caspase family proteins induce cell apoptosis.

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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, Accepted Manuscript
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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, Accepted Manuscript , DOI: 10.1039/C8NJ00697K

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