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

  • Published online on: March 12, 2014     https://doi.org/10.3892/or.2014.3083
  • Pages: 2131-2138
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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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May 2014
Volume 31 Issue 5

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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