Oxoaporphine Metal Complexes (CoII, NiII, ZnII) with High Antitumor Activity by Inducing Mitochondria-Mediated Apoptosis and S-phase Arrest in HepG2

被引：75

作者：

Qin, Jiao-Lan ^{[1
]}

Shen, Wen-Ying ^{[1
]}

Chen, Zhen-Feng ^{[1
]}

Zhao, Li-Fang ^{[1
]}

Qin, Qi-Pin ^{[1
]}

Yu, Yan-Cheng ^{[1
]}

Liang, Hong ^{[1
]}

机构：

[1] Guangxi Normal Univ, Sch Chem & Pharm, State Key Lab Chem & Mol Engn Med Resources, 15 Yucai Rd, Guilin 541004, Peoples R China

来源：

SCIENTIFIC REPORTS | 2017年 / 7卷

基金：

中国国家自然科学基金;

关键词：

G-QUADRUPLEX DNA; VIVO ANTICANCER ACTIVITY; TUMOR-CELL APOPTOSIS; IN-VITRO; TELOMERASE ACTIVITY; CRYSTAL-STRUCTURES; OXIDATIVE STRESS; CYCLE ARREST; DAMAGE; STABILIZATION;

D O I：

10.1038/srep46056

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 mu M. Interestingly, 0.5 mu M 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 release, caspase activation and PARP cleavage. Furthermore, 3 inhibited tumor growth in HepG2 xenograft model, and displayed more safety profile in vivo than cisplatin.

引用

页数：18

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