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

Content Provider	Europe PMC
Author	Gan, Daoju He, Weiyang Yin, Hubin Gou, Xin
Copyright Year	2020
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.
ISSN	17921074
Journal	Oncology Letters
Volume Number	19
PubMed Central reference number	PMC6924103
Issue Number	1
PubMed reference number	31897141
e-ISSN	17921082
DOI	10.3892/ol.2019.11103
Language	English
Publisher	D.A. Spandidos
Publisher Date	2019-11-14
Access Restriction	Open
Rights License	This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. Copyright: © Gan et al.
Subject Keyword	β-elemene cisplatin apoptosis 5′AMP-activated protein kinase bladder cancer
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology