Alajroush Duaa R, Smith Chloe B, Anderson Brittney F, Oyeyemi Ifeoluwa T, Beebe Stephen J, Holder Alvin A
Department of Chemistry and Biochemistry, Old Dominion University 4501 Elkhorn Avenue, Norfolk, VA 23529, U.S.A.
Department of Biological Sciences, University of the Virgin Islands, 2 John Brewers Bay, St. Thomas, VI 00802, U.S.A.
Inorganica Chim Acta. 2024 Mar 1;562. doi: 10.1016/j.ica.2023.121898. Epub 2023 Dec 22.
Metal complexes have gained significant attention as potential anti-cancer agents. The anti-cancer activity of Co(phen)(MeATSC)•1.5HO•CHOH (where phen = 1,10-phenanthroline and MeATSC = 9-anthraldehyde-(4)-methylthiosemicarbazone) and [Cu(acetylethTSC)Cl]Cl•0.25CHOH (where acetylethTSC = -ethyl-2-[1-(thiazol-2-yl)ethylidene]hydrazinecarbothioamide) was investigated by analyzing DNA cleavage activity. The cytotoxic effect was analyzed using CCK-8 viability assay. The activities of caspase 3/7, 9, and 1, reactive oxygen species (ROS) production, cell cycle arrest, and mitochondrial function were further analyzed to study the cell death mechanisms. Complex induced a significant increase in nicked DNA. The IC values of complex were 17.59 μM and 61.26 μM in cancer and non-cancer cells, respectively. The IC values of complex were 5.63 and 12.19 μM for cancer and non-cancer cells, respectively. Complex induced an increase in ROS levels, mitochondrial dysfunction, and activated caspases 3/7, 9, and 1, which indicated the induction of intrinsic apoptotic pathway and pyroptosis. Complex induced cell cycle arrest in the S phase, ROS generation, and caspase 3/7 activation. Thus, complex induced cell death in the breast cancer cell line activation of oxidative stress which induced apoptosis and pyroptosis while complex induced cell cycle arrest through the induction of DNA cleavage.
金属配合物作为潜在的抗癌药物已受到广泛关注。通过分析DNA裂解活性,研究了Co(phen)(MeATSC)•1.5HO•CHOH(其中phen = 1,10 - 菲咯啉,MeATSC = 9 - 蒽醛-(4)-甲基硫代氨基脲)和[Cu(acetylethTSC)Cl]Cl•0.25CHOH(其中acetylethTSC = - 乙基 - 2 - [1 - (噻唑 - 2 - 基)亚乙基]肼基甲硫酰胺)的抗癌活性。使用CCK - 8活力测定法分析细胞毒性作用。进一步分析半胱天冬酶3/7、9和1的活性、活性氧(ROS)生成、细胞周期阻滞和线粒体功能,以研究细胞死亡机制。配合物诱导切口DNA显著增加。配合物在癌细胞和非癌细胞中的IC值分别为17.59 μM和61.26 μM。配合物在癌细胞和非癌细胞中的IC值分别为5.63和12.19 μM。配合物诱导ROS水平升高、线粒体功能障碍,并激活半胱天冬酶3/7、9和1,这表明诱导了内源性凋亡途径和细胞焦亡。配合物诱导细胞周期阻滞于S期、ROS生成和半胱天冬酶3/7激活。因此,配合物通过诱导氧化应激激活凋亡和细胞焦亡,从而在乳腺癌细胞系中诱导细胞死亡,而配合物通过诱导DNA裂解诱导细胞周期阻滞。