title: β-elemene reverses the drug resistance of A549/DDP lung cancer cells by activating intracellular redox system, decreasing mitochondrial membrane potential and P-glycoprotein expression, and inducing apoptosis.
abstract: β-elemene (β-ELE) injection is a new anticancer drug extracted from Curcuma zedoaria Roscoe that has been widely used to treat malignant tumors. Recent studies show that β-ELE reverses the drug resistance of tumor cells. To explore the possible mechanisms of β-ELE, we investigated its effects on cisplatin (DDP)-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, flow cytometry with Annexin V-FITC/propium iodide double staining; mitochondrial membrane potential using JC-1 fluorescence probe and laser confocal scanning microscopy, and intracellular reactive oxygen species levels were measured by 2',7'-dichlorfluorescein-diacetate staining and flow cytometry; and contents of cytosolic glutathione were determined by glutathione assay kits. Intracellular Rhodamine-123 fluorescence intensity was detected by flow cytometry, and the expression of P-glycoprotein (P-gp) was detected by Western blotting.
  
  
  
  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 intracellular accumulation of Rhodamine-123, decreased the cytoplasmic glutathione levels and the expression of P-gp in a time- and dose-dependent manner.
  
  
  
  These results define a pathway of β-ELE function that involves decreased mitochondrial membrane potential and P-gp expression activated intracellular redox system, and induced apoptosis leading to reverse drug resistance.
authors.affiliation: Department of Thoracic Surgery, the First Affiliated Hospital of Fujian Medical University Fuzhou, China; Department of Thoracic Surgery, Xiamen Traditional Chinese Medicine (TCM) Hospital of Fujian University of TCM Xiamen, China.
authors.forename: Chengcai
authors.initials: C
authors.lastname: Yao
authors.affiliation: Department of Thoracic Surgery, the First Affiliated Hospital of Xiamen University Xiamen, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Thoracic Surgery, the First Affiliated Hospital of Fujian Medical University Fuzhou, China.
authors.forename: Yuanrong
authors.initials: Y
authors.lastname: Tu
authors.affiliation: College of Molecular Biology and Material, Xiamen University Xiamen, China.
authors.forename: Shefang
authors.initials: S
authors.lastname: Ye
authors.affiliation: Department of Thoracic Surgery, Xiamen Traditional Chinese Medicine (TCM) Hospital of Fujian University of TCM Xiamen, China.
authors.forename: Haoxin
authors.initials: H
authors.lastname: Du
authors.affiliation: Department of Thoracic Surgery, Xiamen Traditional Chinese Medicine (TCM) Hospital of Fujian University of TCM Xiamen, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
keywords: A549/DDP cell; apoptosis; drug resistance; elemene; lung neoplasms