β‑elemene enhances cisplatin‑induced apoptosis in bladder cancer cells through the ROS‑AMPK signaling pathway

Gan,Daoju; He,Weiyang; Yin,Hubin; Gou,Xin

doi:10.3892/ol.2019.11103

β‑elemene enhances cisplatin‑induced apoptosis in bladder cancer cells through the ROS‑AMPK signaling pathway

Authors:
- Daoju Gan
- Weiyang He
- Hubin Yin
- Xin Gou
View Affiliations

Affiliations: Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China
Published online on: November 14, 2019 https://doi.org/10.3892/ol.2019.11103
Pages: 291-300
Copyright: © Gan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cisplatin‑based chemotherapy is the standard regimen for patients with bladder cancer, but its effectiveness is limited by high toxicity and the development of drug resistance. β‑elemene (β‑ELE), a compound extracted from Rhizoma zedoariae, has antitumor activity in various malignancies and exhibits low toxicity. However, the effects and specific mechanism of β‑ELE in bladder cancer remain unclear. The present study aimed to investigate the antitumor activity and possible mechanisms of β‑ELE alone and in combination with cisplatin in bladder cancer cells. Cell viability was determined using Cell Counting Kit‑8. Cell cycle and reactive oxygen species (ROS) analyses were performed by flow cytometry. Apoptosis was detected by Hoechst 33258 and Annexin‑V/propidium iodide staining. Mitochondrial membrane potential was determined by staining with a JC‑1 probe, flow cytometry and fluorescence microscopy. Protein expression was detected by western blotting. The results revealed that β‑ELE significantly inhibited the proliferation of various bladder cancer cell lines and induced cell cycle arrest at G0/G1‑phase in T24 and 5637 cells. Compared with cisplatin alone, co‑treatment with β‑ELE increased cisplatin‑mediated cytotoxicity against T24 cells, which resulted in the loss of mitochondrial membrane potential and release of cytochrome c into the cytoplasm. Co‑treatment with β‑ELE and cisplatin enhanced ROS accumulation and activation of 5'AMP‑activated protein kinase (AMPK), which induced apoptosis. The results of the present study suggested that β‑ELE inhibited the proliferation of bladder cancer cells in vitro and enhanced cisplatin‑induced mitochondria‑dependent apoptosis via the ROS‑AMPK signaling pathway. Combination therapy with β‑ELE requires further investigation as a potential treatment of bladder cancer.

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