Diethyl (6-amino-9H-purin-9-yl) methylphosphonate induces apoptosis and cell cycle arrest in hepatocellular carcinoma BEL-7402 cells: Role of reactive oxygen species

• Published in: Free radical research 2010-08, Vol.44 (8), p.881-890
• Main Authors: Qu, Bin, Wang, Wei, Tan, Zhenyi, Li, Di, Wan, Jun, Sun, Jie, Cheng, Kun, Luo, Hao
• Format: Article
• Language: English
• Subjects: Acyclic nucleoside phosphonate; Antineoplastic Agents - pharmacology; apoptosis; Apoptosis - drug effects; Caspase 3 - metabolism; Caspase 9 - metabolism; Cell Cycle - drug effects; Cell Proliferation - drug effects; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Free Radical Scavengers - metabolism; Humans; Organophosphonates - pharmacology; oxidative stress; Purines - pharmacology; reactive oxygen species (ROS); Reactive Oxygen Species - metabolism; S Phase - drug effects; Tumor Cells, Cultured; vitamin C
• ISSN: 1071-5762; 1029-2470
• DOI: 10.3109/10715762.2010.487868

Abstract The primary purpose of this work was to study the mechanism of the anti-proliferation activity of compound diethyl (6-amino-9H-purin-9-yl) methylphosphonate (DaMP), a novel acyclic nucleoside phosphonate. Using cell survival MTT assay, flow cytometry analysis, DNA laddering, DCF fluorescence detection and caspases assays, this study investigated the effects of this compound on cell apoptosis, cell cycle regulation and reactive oxygen species in human hepatocarcinoma BEL-7402 cell lines. Exposure to DaMP at 80 μM for 24 h, BEL-7402 cells displayed a marked retardation of S-phase progression, leading to a severe perturbation of normal cell cycle. In addition, DaMP also significantly inhibited cell proliferation by inducing apoptosis, disrupting DNA synthesis and increasing the activities of caspase-3 and -9, while the antioxidants could significantly inhibit these effects. This study was the first to demonstrate that DaMP could induce apoptosis and cell cycle arrest by producing reactive oxygen species and activating caspase-3 and -9.