Gallium(iii)–2-benzoylpyridine-thiosemicarbazone complexes promote apoptosis through Ca2+ signaling and ROS-mediated mitochondrial pathways. (25th May 2018)

• Record Type: Journal Article
• Authors: Qi, Jinxu; Qian, Kun; Tian, Liang; Cheng, Zhen; Wang, Yihong
• Is Part Of: New journal of chemistry. Volume 42:Number 12(2018)
• Page Start: 10226
• Page End: 10233
• Publication Date: 2018-05-25
• Subjects: Chemistry -- Periodicals; Chimie -- Périodiques; 540
• DOI: 10.1039/c8nj00697k
• Languages: English
• ISSNs: 1144-0546

Abstract

Abstract : Ga(iii ) complexes promoted apoptosis as a result of a combination of multiple apoptotic pathways. 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 wasC3, which exhibited a better antitumor viability than its related ligands and the anticancer agent3-AP . Thus, the Ga(iii ) complexes not only transmitted the iron ions but also induced intracellular Ca 2+ 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.