A 9-chloro-5,6,7,8-tetrahydroacridine Pt(II) complex induces apoptosis of Hep-G2 cells via inhibiting telomerase activity and disrupting mitochondrial pathway

摘要

In the present study, one novel Pt(II) complex, (Pt(CTD)(DMSO)Cl-2] (1) with 9-chloro-5,6,7,8-tetrahy-droacridine (CTD) as ligand, was synthesized and fully characterized. The CTD Pt(II) complex 1 was an anticancer drug candidate, and it possessed potent therapeutic efficacy for hepatocellular carcinoma (HCC). To explore its mechanism against HCC, Hep-G2 cells were treated with the CTD Pt(II) complex 1 in vitro. mu assay showed that the CTD POD complex 1 had inhibitory activity against five human cancer cells, such as SK-OV-3, Hep-G2, NCI-H460, MGC80-3 and HL-7702, and it displayed the strongest inhibitory activity against Hep-G2 cells with an 1050 value of 10.48 +/- 0.83 mu M. Moreover, the CTD Pt(II) complex 1 also exhibited selective cytotoxicity toward the cancer cells. In addition, the CTD Pt(11) complex 1 had low toxicity against non-cancerous HL-7702 cells. The CTD Pt(II) complex 1 caused mitochondrial dysfunction, leading to the down-regulation of bcl-2 protein and up-regulation of some mitochondria-initiated apoptotic proteins (including apaf-1, cytochrome c and bax) in Hep-G2 cells. Taken together, the CTD Pt(II) complex 1-triggered Hep-G2 cell apoptosis was mainly mediated via interaction with c-myc promoter and disruption of mitochondrial pathway. Collectively, on findings supported that the CTD Pt(II) complex 1 could be used as a potential drug candidate for chemopre vention or chemotherapy of HCC.