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Article

β-elemene reverses the drug resistance of lung cancer A549/DDP cells via the mitochondrial apoptosis pathway

  • Authors:
    • Cheng-Cai Yao
    • Yuan-Rong Tu
    • Jie Jiang
    • Sheng-Fang Ye
    • Hao-Xin Du
    • Yi Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Thoracic Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 355000, P.R. China, Department of Thoracic Surgery, The First Affiliated Hospital of Xiamen University, Xiamen 361001, P.R. China, College of Molecular Biology and Material of Xiamen University, Xiamen 361000, P.R. China, Department of Thoracic Surgery, Xiamen Traditional Chinese Medicine (TCM) Hospital Affiliated to Fujian University of TCM, Xiamen 361009, P.R. China
  • Pages: 2131-2138
    |
    Published online on: March 12, 2014
       https://doi.org/10.3892/or.2014.3083
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Abstract

β-elemene (β-ELE) is a new anticancer drug extracted from Curcuma zedoaria Roscoe and has been widely used to treat malignant tumors. Recent studies have demonstrated that β-ELE reverses the drug resistance of tumor cells. To explore the possible mechanisms of action of β-ELE, we investigated its effects on cisplatin-resistant human lung adenocarcinoma A549/DDP cells. The effects of β-ELE on the growth of A549/DDP cells in vitro were determined by MTT assay. Apoptosis was assessed by fluorescence microscopy with Hoechst 33258 staining and flow cytometry with Annexin V-FITC/PI double staining. Mitochondrial membrane potential was assessed using JC-1 fluorescence probe and laser confocal scanning microscopy, and intracellular reactive oxygen species levels were measured by 2',7'-dichlorofluorescein-diacetate staining and flow cytometry. Cytosolic glutathione content was determined using GSH kits. The expression of cytochrome c, caspase-3, procaspase-3 and the Bcl-2 family proteins was assessed by western blotting. The results demonstrated that β-ELE inhibited the proliferation of A549/DDP cells in a time- and dose-dependent manner. Furthermore, β-ELE enhanced the sensitivity of A549/DDP cells to cisplatin and reversed the drug resistance of A549/DDP cells. Consistent with a role in activating apoptosis, β-ELE decreased mitochondrial membrane potential, increased intracellular reactive oxygen species concentration and decreased the cytoplasmic glutathione levels in a time- and dose-dependent manner. The combination of β-ELE and cisplatin enhanced the protein expression of cytochrome c, caspase-3 and Bad, and reduced protein levels of Bcl-2 and procaspase-3 in the A549/DDP lung cancer cells. These results define a pathway of procaspase‑3-β-ELE function that involves decreased mitochondrial membrane potential, leading to apoptosis triggered by the release of cytochrome c into the cytoplasm and the modulation of apoptosis-related genes. The reversal of drug resistance of the A549/DDP cell line by β-ELE may be derived from its effect in inducing apoptosis.
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Copy and paste a formatted citation
Spandidos Publications style
Yao C, Tu Y, Jiang J, Ye S, Du H and Zhang Y: β-elemene reverses the drug resistance of lung cancer A549/DDP cells via the mitochondrial apoptosis pathway. Oncol Rep 31: 2131-2138, 2014.
APA
Yao, C., Tu, Y., Jiang, J., Ye, S., Du, H., & Zhang, Y. (2014). β-elemene reverses the drug resistance of lung cancer A549/DDP cells via the mitochondrial apoptosis pathway. Oncology Reports, 31, 2131-2138. https://doi.org/10.3892/or.2014.3083
MLA
Yao, C., Tu, Y., Jiang, J., Ye, S., Du, H., Zhang, Y."β-elemene reverses the drug resistance of lung cancer A549/DDP cells via the mitochondrial apoptosis pathway". Oncology Reports 31.5 (2014): 2131-2138.
Chicago
Yao, C., Tu, Y., Jiang, J., Ye, S., Du, H., Zhang, Y."β-elemene reverses the drug resistance of lung cancer A549/DDP cells via the mitochondrial apoptosis pathway". Oncology Reports 31, no. 5 (2014): 2131-2138. https://doi.org/10.3892/or.2014.3083
Copy and paste a formatted citation
x
Spandidos Publications style
Yao C, Tu Y, Jiang J, Ye S, Du H and Zhang Y: β-elemene reverses the drug resistance of lung cancer A549/DDP cells via the mitochondrial apoptosis pathway. Oncol Rep 31: 2131-2138, 2014.
APA
Yao, C., Tu, Y., Jiang, J., Ye, S., Du, H., & Zhang, Y. (2014). β-elemene reverses the drug resistance of lung cancer A549/DDP cells via the mitochondrial apoptosis pathway. Oncology Reports, 31, 2131-2138. https://doi.org/10.3892/or.2014.3083
MLA
Yao, C., Tu, Y., Jiang, J., Ye, S., Du, H., Zhang, Y."β-elemene reverses the drug resistance of lung cancer A549/DDP cells via the mitochondrial apoptosis pathway". Oncology Reports 31.5 (2014): 2131-2138.
Chicago
Yao, C., Tu, Y., Jiang, J., Ye, S., Du, H., Zhang, Y."β-elemene reverses the drug resistance of lung cancer A549/DDP cells via the mitochondrial apoptosis pathway". Oncology Reports 31, no. 5 (2014): 2131-2138. https://doi.org/10.3892/or.2014.3083
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