A Pyrazolate Osmium(VI) Nitride Exhibits Anticancer Activity Through Modulating Protein Homeostasis in HepG2 Cells

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2022 Nov 11

PMID 36361570

Authors

Chengyang Huang

Wanqiong Huang

Pengchao Ji

Fuling Song

Tao Liu

Meiyang Li

Hongzhi Guo

Yongliang Huang

Cuicui Yu

Chuanxian Wang

Wenxiu Ni

Affiliations

Soon will be listed here.

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 (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.

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