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Antitumor effect of a copper (II) complex of a coumarin derivative and phenanthroline on lung adenocarcinoma cells and the mechanism of action.
- Source :
-
Molecular medicine reports [Mol Med Rep] 2014 Nov; Vol. 10 (5), pp. 2477-82. Date of Electronic Publication: 2014 Aug 26. - Publication Year :
- 2014
-
Abstract
- In order to investigate the effect of a copper (II) complexes of a coumarin derivative and phenanthroline (hereinafter referred to as the coumarin-copper drug) on lung adenocarcinoma cells in vivo and in vitro, along with the mechanism of action, LA795 lung adenocarcinoma cells were treated with different concentrations of coumarin-copper drug. An MTT assay was performed to determine the cell proliferation ratio, cell apoptosis was detected by Annexin V/propidium iodide staining with flow cytometric analysis and western blot analysis was employed to evaluate the expression levels of apoptosis-associated proteins. In addition, an LA795 cell xenograft tumor model was established in nude mice, with mice receiving intraperitoneal injection once a week for three weeks of either 2 or 4 mg/kg in three divided doses coumarin‑copper drug, or phosphate‑buffered saline. The tumor growth curves were drawn and the tumor growth inhibition rates were calculated. The apoptotic index of subcutaneously transplanted tumor cells was determined by terminal deoxynucleotidyl‑transferase‑mediated dUTP nick end‑labeling assay. The coumarin-copper drug effectively inhibited the proliferation of LA795 cells in a dose‑ and time‑dependent manner, with the half maximal inhibitory concentration equaling 2.0 µmol/l. The coumarin-copper drug also significantly induced LA795 cell apoptosis in a time-dependent manner (P<0.05), which was accompanied by upregulation p35 and B-cell lymphoma-2 (Bcl-2)-associated X protein (Bax), and downregulation of Bcl-2. Furthermore, the coumarin‑copper drug significantly inhibited the growth of LA795 tumors in a dose dependent manner (P<0.05), in accordance with the apoptotic index. In conclusion, the coumarin-copper drug may inhibit the proliferation of LA795 cells through the induction of cell apoptosis, which may be associated with the upregulation of p53 and Bax, with concurrent downregulation of Bcl-2.
- Subjects :
- Adenocarcinoma metabolism
Adenocarcinoma pathology
Animals
Apoptosis drug effects
Cell Line, Tumor
Cell Survival drug effects
Female
Humans
Lung Neoplasms metabolism
Lung Neoplasms pathology
Mice, Nude
Proto-Oncogene Proteins c-bcl-2 metabolism
Tumor Burden drug effects
Tumor Suppressor Protein p53 metabolism
Xenograft Model Antitumor Assays
bcl-2-Associated X Protein metabolism
Adenocarcinoma drug therapy
Antineoplastic Agents pharmacology
Coordination Complexes pharmacology
Coumarins pharmacology
Lung Neoplasms drug therapy
Phenanthrolines pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1791-3004
- Volume :
- 10
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Molecular medicine reports
- Publication Type :
- Academic Journal
- Accession number :
- 25176185
- Full Text :
- https://doi.org/10.3892/mmr.2014.2519