A β-carboline derivative-based nickel(ii) complex as a potential antitumor agent: synthesis, characterization, and cytotoxicity12. Issue 1 (24th November 2017)

• Record Type: Journal Article
• Authors: Yang, Jing-Mei; Zhu, Yan-Hong; Chen, Sheng; Lu, Xing; Wu, Yi-Ming; Ma, Feng-E; Li, Liang-Ping; Yang, Yang; Shi, Zhen-Hao; Huang, Kun-Yuan; Hong, Xue; Jiang, Ping; Peng, Yan
• Is Part Of: MedChemComm. Volume 9:Issue 1(2018)
• Page Start: 100
• Page End: 107
• Publication Date: 2017-11-24
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19
• DOI: 10.1039/c7md00428a
• Languages: English
• ISSNs: 2040-2503

Abstract

Abstract : A novel nickel(ii ) complex was synthesized and characterized. It significantly induced cell cycle arrest at S phase, and caused the down-regulation of p-AKT, cyclin E, cyclin A and CDK2 and the up-regulation of p27. Abstract : A novel nickel(ii ) complex of 6-methoxy-1-pyridine-β-carboline (4a ) was synthesized and characterized. The cytotoxicities of the complex towards six cancer cell lines, including MGC-803, Hep G2, T24, OS-RC-2, NCI-H460, and SK-OV-3, and human normal liver cell line HL-7702 were investigated. The IC50 values for MGC-803, Hep G2, T24, OS-RC-2, NCI-H460 and SK-OV-3 were generally in the micromolar range (3.77–15.10 μM), lower than those of ligand4 and cisplatin. Furthermore, 4a (6 μM) significantly induced cell cycle arrest at the S phase, and caused the down-regulation of p-AKT, cyclin E, cyclin A and CDK2 and the up-regulation of p27. Various experiments showed that4a induced apoptosis, activated caspase-3, increased the levels of reactive oxygen species (ROS) and enhanced the intracellular [Ca 2+ ]c levels in MGC-803. In addition, the expression of intrinsic apoptotic proteins, including cytochrome c and apaf-1, increased. Further intrinsic apoptosis was triggered via executive molecular caspase-9 and caspase-3. In short, 4a exerted its cytotoxic activity primarily through inducing cell cycle arrest at the S phase and intrinsic apoptosis.