We report a new osmium(VI) nitrido complex bearing a nonplanar tetradentate ligand with potent anticancer activity. It causes mitochondrial damage, which induces liver cancer cell death via oncosis and apoptosis....

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 Na[OsVI(N)(tpm)2] (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 Na[OsVI(N)(tpm)2] 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.

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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 Na[OsVI(N)(tpm)2] (tpm= [5-(Thien-2-yl)-1H-pyrazol-3-yl]methanol) that does not have direct binding affinity to DNA. Cellular assays revealed that this new Os complex exhibited anticancer activity against cancer cell lines, cancer stem cells, and cisplatin-resistant cells. The Os complex Na[OsVI(N)(tpm)2] 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 Os complex in cancer cells affects the functions of the mitochondria and endoplasmic reticulum, resulting in high levels of cellular oxidative stress and low rates of cell survival. Moreover, it induced caspase-mediated apoptosis of HepG2 cancer cells. The study reveals a new high-valent Os complex as an anticancer agent candidate targeting cancer cell protein homeostasis.

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