Oxoaporphine Metal Complexes (Co^II, Ni^II, Zn^II) with High Antitumor Activity by Inducing Mitochondria-Mediated Apoptosis and S-phase Arrest in HepG2.

ABSTRACT: Three new oxoaporphine Co(II), Ni(II) and Zn(II) complexes 1-3 have been synthesized and fully characterized. 1-3 have similar mononuclear structures with the metal and ligand ratio of 1:2. 1-3 exhibited higher cytotoxicity than the OD ligand and cisplatin against HepG2, T-24, BEL-7404, MGC80-3 and SK-OV-3/DDP cells, with IC₅₀ value of 0.23-4.31 μM. Interestingly, 0.5 μM 1-3 significantly caused HepG2 arrest at S-phase, which was associated with the up-regulation of p53, p21, p27, Chk1 and Chk2 proteins, and decrease in cyclin A, CDK2, Cdc25A, PCNA proteins. In addition, 1-3 induced HepG2 apoptosis via a caspase-dependent mitochondrion pathway as evidenced by p53 activation, ROS production, Bax up-regulation and Bcl-2 down-regulation, mitochondrial dysfunction, cytochrome c rele

SUBMITTER: Qin JL 

PROVIDER: S-EPMC5402304 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature