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Effect of dicycloplatin, a novel platinum chemotherapeutical drug, on inhibiting cell growth and inducing cell apoptosis.
- Source :
-
PloS one [PLoS One] 2012; Vol. 7 (11), pp. e48994. Date of Electronic Publication: 2012 Nov 12. - Publication Year :
- 2012
-
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.
- Subjects :
- Antineoplastic Agents chemistry
Antineoplastic Agents toxicity
Caspase 3 metabolism
Caspase 8 metabolism
Cell Line, Tumor
Cell Proliferation drug effects
Drug Combinations
Gene Expression Regulation, Neoplastic
Hep G2 Cells
Humans
Membrane Potential, Mitochondrial drug effects
Models, Biological
Platinum chemistry
Platinum toxicity
Poly(ADP-ribose) Polymerases metabolism
Reactive Oxygen Species metabolism
Receptors, Death Domain metabolism
Signal Transduction drug effects
Tumor Suppressor Protein p53 genetics
Tumor Suppressor Protein p53 metabolism
Antineoplastic Agents pharmacology
Apoptosis drug effects
Glutamates pharmacology
Organoplatinum Compounds pharmacology
Platinum pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 7
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 23152837
- Full Text :
- https://doi.org/10.1371/journal.pone.0048994