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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.
- Source :
-
Free radical research [Free Radic Res] 2010 Aug; Vol. 44 (8), pp. 881-90. - Publication Year :
- 2010
-
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 microM 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.
- Subjects :
- 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
S Phase drug effects
Tumor Cells, Cultured
Antineoplastic Agents pharmacology
Apoptosis drug effects
Organophosphonates pharmacology
Purines pharmacology
Reactive Oxygen Species metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1029-2470
- Volume :
- 44
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Free radical research
- Publication Type :
- Academic Journal
- Accession number :
- 20528564
- Full Text :
- https://doi.org/10.3109/10715762.2010.487868