Beta-elemene enhances cisplatin-induced apoptosis in bladder cancer cells. - GreenMedInfo Summary
β-elemene enhances cisplatin-induced apoptosis in bladder cancer cells through the ROS-AMPK signaling pathway.
Oncol Lett. 2020 Jan ;19(1):291-300. Epub 2019 Nov 14. PMID: 31897141
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, has antitumor activity in various malignancies and exhibits low toxicity. However, the effects and specific mechanism ofβ-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 G/G-phase in T24 and 5637 cells. Compared with cisplatin alone, co-treatment withβ-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 cellsand enhanced cisplatin-induced mitochondria-dependent apoptosis via the ROS-AMPK signaling pathway. Combination therapy withβ-ELE requires further investigation as a potential treatment of bladder cancer.