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Abstract In the present study, one novel Pt(II) complex, [Pt(CTD)(DMSO)Cl 2 ] (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 IC 50 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. Graphical abstract The CTD Pt(II) complex 1 triggered Hep‑G2 cell apoptosis mainly through inhibiting telomerase activity by interacting with c‑myc promoter elements and disruption of mitochondrial pathway. Unlabelled Image Highlights • The CTD Pt(II) complex 1 with 9‑chloro‑5,6,7,8‑tetrahydroacridine was designed and synthesized. • The CTD Pt(II) complex 1 was more selective for Hep‑G2 tumor cells versus normal cells (HL‑7702). • The CTD Pt(II) complex 1 was a potent inhibitor of telomerase. • The CTD Pt(II) complex 1 also caused mitochondrial dysfunction. [ABSTRACT FROM AUTHOR]

Abstract A dinuclear palladium(II) complex, [Pd 2 (μ ‑OAc‑ κ O,O) 2 (phpy‑ κ N,C) 2 ] (1), with 2‑phenylpyridine (H‑phpy) as a ligand was synthesized and characterized by IR, ESI-MS, single-crystal X-ray diffraction, and elemental analysis. By the MTT assay, the dinuclear palladium(II) complex 1 showed lower cytotoxic activity toward normal HL-7702 cells (IC 50 = 85.89 ± 0.89 μM). However, it displayed high cytotoxicity against SK-OV-3, NCI-H460, T-24, and HeLa cells, with IC 50 values of 5.50 ± 1.08, 0.46 ± 0.28, 7.93 ± 1.16 and 0.35 ± 0.29 μM, respectively. Importantly, we found that this Pd(II) complex exhibited lower toxicity and better anticancer activity than that of cisplatin. Further cellular assays, including Western blotting and flow cytometry, gave evidence that apoptosis after treatment with the dinuclear palladium(II) complex 1 may be induced by the intrinsic mitochondrial dysfunction pathway. Graphical abstract Apoptosis after treatment with the dinuclear palladium(II) complex 1 may be induced by the intrinsic mitochondrial dysfunction pathway. Unlabelled Image Highlights • Synthesis of the dinuclear palladium(II) complex 1 was reported. • The dinuclear palladium(II) complex 1 was more cytotoxic than cisplatin in all the cell lines tested. • The dinuclear palladium(II) complex 1 could induce mitochondrial dysfunction. [ABSTRACT FROM AUTHOR]

Abstract: Three mononuclear silver(I) complexes with 8-hydroxyquinoline, 8-hydroxy-2-methylquinoline and 5-chloro-8-quinolinol were synthesized and characterized by elemental analysis, NMR, ESI-MS as well as single crystal X-ray diffraction analysis. All the structures of complexes 1–3 with the silver center adopting an approximately four-coordinated distorted tetragonal pyramid geometry were found to exhibit selective cytotoxicity against HepG2, NCI-H460, BEL-7404 and HeLa cell lines with IC50 values generally in the micromolar range (1.7–14.6μM), but low cytotoxicity towards normal human liver cell HL-7702. A combination of flow cytometric analysis and molecular probe observation indicated that complexes 1–3 could induce HepG2 cell apoptosis. Molecular mechanism studies suggested that complexes 1–3-induced apoptosis is mediated through the intrinsic apoptotic pathway with changes in mitochondrial membrane potential by finally activating effector caspase-3/9 to trigger cell apoptosis. Further studies revealed that complexes 1 and 2 caused cell cycle arrest at S phase, while complex 3 induced G1 cell cycle arrest in HepG2 cells. Taken together, these results suggest that complexes 1–3 may be potential candidates for cancer therapy. [Copyright &y& Elsevier]