title: Effect of dicycloplatin, a novel platinum chemotherapeutical drug, on inhibiting cell growth and inducing cell apoptosis.
abstract: Dicycloplatin, a new supramolecular platinum-based antitumor drug, has been approved by the State Food and Administration (SFDA) of China. In this study, we investigated the anticancer activity of dicycloplatin in cancer cells and signaling pathways involved in dicycloplatin-induced apoptosis. Dicycloplatin inhibited the proliferation of cancer cells and increased the percentage of apoptosis in a concentration-dependent manner. Besides, some apoptosis related events were observed after treatment with dicycloplatin, including increase of reactive oxygen species (ROS), collapse of mitochondrial membrane potential (Δψm), release of cytochrome c from the mitochondria to the cytosol, upregulation of p53, which were accompanied by activation of caspase-9, caspase-3, caspase-8, and poly (ADP-ribose) polymerase cleavage in a concentration-dependent manner. The role of apoptosis in dicycloplatin-mediated cell death was further confirmed by the concomitant treatment with caspase-8 or caspase-9 inhibitors, which inhibited apoptosis and PARP cleavage. Intracellular glutathione (GSH) was also found to inhibit the cytotoxic effect of dicycloplatin. In conclusion, these findings suggest that dicycloplatin induces apoptosis through ROS stress-mediated death receptor pathway and mitochondrial pathway which is similar to carboplatin.
authors.affiliation: Department of General Surgery, Chen Xing Hai Hosital, Guangdong Medical College, Zhongshan, People's Republic of China.
authors.forename: Guang-quan
authors.initials: GQ
authors.lastname: Li
authors.forename: Xing-gui
authors.initials: XG
authors.lastname: Chen
authors.forename: Xing-ping
authors.initials: XP
authors.lastname: Wu
authors.forename: Jing-dun
authors.initials: JD
authors.lastname: Xie
authors.forename: Yong-ju
authors.initials: YJ
authors.lastname: Liang
authors.forename: Xiao-qin
authors.initials: XQ
authors.lastname: Zhao
authors.forename: Wei-qiang
authors.initials: WQ
authors.lastname: Chen
authors.forename: Li-wu
authors.initials: LW
authors.lastname: Fu
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004338:Drug Combinations; D015972:Gene Expression Regulation, Neoplastic; D005971:Glutamates / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008954:Models, Biological; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D010984:Platinum / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D053218:Receptors, Death Domain / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D004338:Drug Combinations; D005971:Glutamates; D009944:Organoplatinum Compounds; D017382:Reactive Oxygen Species; D053218:Receptors, Death Domain; D016159:Tumor Suppressor Protein p53; C580746:diammine(1,1-cyclobutanedicarboxylate)platinum(II); D010984:Platinum; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D053181:Caspase 8