Department of Physiology, Shantou University Medical College, Shantou 515041, China.
Department of Biological Chemistry, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
Int J Mol Sci. 2022 Oct 24;23(21):12779. doi: 10.3390/ijms232112779.
Interest in the third-row transition metal osmium and its compounds as potential anticancer agents has grown in recent years. Here, we synthesized the osmium(VI) nitrido complex (tpm = [5-(Thien-2-yl)-1H-pyrazol-3-yl]methanol), which exhibited a greater inhibitory effect on the cell viabilities of the cervical, ovarian, and breast cancer cell lines compared with cisplatin. Proteomics analysis revealed that modulates the expression of protein-transportation-associated, DNA-metabolism-associated, and oxidative-stress-associated proteins in HepG2 cells. Perturbation of protein expression activity by the complex in cancer cells affects the functions of the mitochondria, resulting in high levels of cellular oxidative stress and low rates of cell survival. Moreover, it caused G2/M phase cell cycle arrest and caspase-mediated apoptosis of HepG2 cells. This study reveals a new high-valent osmium complex as an anticancer agent candidate modulating protein homeostasis.
近年来，人们对作为潜在抗癌药物的第三过渡金属锇及其化合物产生了浓厚的兴趣。在这里，我们合成了六价锇（VI）亚硝化物配合物 （tpm = [5-(噻吩-2-基)-1H-吡唑-3-基]甲醇），与顺铂相比，它对宫颈、卵巢和乳腺癌细胞系的细胞活力表现出更大的抑制作用。蛋白质组学分析表明， 调节 HepG2 细胞中与蛋白转运、DNA 代谢和氧化应激相关的蛋白的表达。该复合物在癌细胞中对蛋白表达活性的干扰会影响线粒体的功能，导致细胞内氧化应激水平升高和细胞存活率降低。此外，它还导致 HepG2 细胞发生 G2/M 期细胞周期阻滞和 caspase 介导的细胞凋亡。本研究揭示了一种新型高价锇配合物作为一种调节蛋白动态平衡的抗癌药物候选物。
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