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

Abstract

In the present study, one novel Pt(II) complex, [Pt(CTD)(DMSO)Cl2] (1) with 9‑chloro‑5,6,7,8‑tetrahydroacridine (CTD) as ligand, was synthesized and fully characterized. The CTD Pt(II) complex 1 was an anti-cancer 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. MTT assay showed that the CTD Pt(II) 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 IC50 value of 10.48 ± 0.83 μM. Moreover, the CTD Pt(II) complex 1 also exhibited selective cytotoxicity toward the cancer cells. In addition, the CTD Pt(II) 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, our findings supported that the CTD Pt(II) complex 1 could be used as a potential drug candidate for chemoprevention or chemotherapy of HCC.