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

Thoracic Cancer

Chengcai Yao¹  Jie Jiang⁴  Yuanrong Tu¹  Shefang Ye²  Haoxin Du³ 

[1] Department of Thoracic Surgery, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China;College of Molecular Biology and Material, Xiamen University, Xiamen, China;Department of Thoracic Surgery, Xiamen Traditional Chinese Medicine (TCM) Hospital of Fujian University of TCM, Xiamen, China;Department of Thoracic Surgery, the First Affiliated Hospital of Xiamen University, Xiamen, China

关键词: A549/DDP cell;    apoptosis;    drug resistance;    elemene;    lung neoplasms;   

DOI  :  10.1111/1759-7714.12093

来源: Wiley

【 摘 要 】

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.

【 授权许可】

Unknown   
© 2014 Tianjin Lung Cancer Institute and Wiley Publishing Asia Pty Ltd