A New Pyrazolate Osmium(VI) Nitrido Complex Exhibits Anticancer Activity Through Modulating Protein Homeostasis

Abstract 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.