Antitumor effect of a copper (II) complex of a coumarin derivative and phenanthroline on lung adenocarcinoma cells and the mechanism of action

Zhu,Taofeng; Chen,Ruhua; Yu,Hao; Feng,Yan; Chen,Jianqiang; Lu,Qin; Xie,Jing; Ding,Weiliang; Ma,Tieliang

doi:10.3892/mmr.2014.2519

Antitumor effect of a copper (II) complex of a coumarin derivative and phenanthroline on lung adenocarcinoma cells and the mechanism of action

Authors:
- Taofeng Zhu
- Ruhua Chen
- Hao Yu
- Yan Feng
- Jianqiang Chen
- Qin Lu
- Jing Xie
- Weiliang Ding
- Tieliang Ma
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Affiliations: Department of Respiratory Medicine, The Affiliated Yixing Hospital of Jiangsu University, Yixing, Jiangsu 214200, P.R. China, Department of Respiratory Medicine, The Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu 212002, P.R. China, Department of Geriatrics, The Affiliated Yixing Hospital of Jiangsu University, Yixing, Jiangsu 214200, P.R. China, Central Laboratory, The Affiliated Yixing Hospital of Jiangsu University, Yixing, Jiangsu 214200, P.R. China
Published online on: August 26, 2014 https://doi.org/10.3892/mmr.2014.2519
Pages: 2477-2482

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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.

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