Role of mitochondrial permeability transition in human hepatocellular carcinoma Hep-G2 cell death induced by rhein |
| |
| Institution: | 1. Department of Pharmacy, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai 200032, China;2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China;3. Department of Pharmacy, Luwan Branch of Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;4. Department of Pharmacy, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;1. Centre for Neuroinflammation & Neurodegeneration, Division of Brain Sciences, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, United Kingdom;2. Department of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne NE1 8ST, United Kingdom;3. Matrilinex LLC, San Diego, CA 92122, USA;4. Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne NE1 3BZ, United Kingdom;5. Centre for Human Metabonomics, North-West University, Potchefstroom, South Africa;6. Department of Radiation Therapy, UTMB, Galveston, TX, United States |
| |
| Abstract: | Rhein, a compound found as a glucoside in the root of rhubarb, is currently a subject of interest for its antitumor properties. The apoptosis of tumor cell lines induced by rhein was observed, and the involvement of mitochondria was established; however, the role of mitochondrial permeability transition (MPT) remains unknown. Here we report that MPT plays an important role in the apoptosis of human hepatocellular carcinoma Hep-G2 cells induced by rhein. After adding rhein to the isolated hepatic mitochondria, swelling effects and the leakage of Ca2 + were observed. These alterations were suppressed by cyclosporin A (CsA), an MPT inhibitor. Furthermore, in Hep-G2 cells, the decrease of ATP production, the loss of mitochondrial transmembrane potential (MTP), the release of cytochrome c (Cyto c), and the activation of caspase 3 were also observed. These toxic effects of rhein can also be attenuated by CsA as well. Moreover, TUNEL assay confirmed that in the presence of CsA, rhein-induced apoptosis was largely inhibited. These results suggest that MPT plays a critical role in the pathogenesis of Hep-G2 cell injury induced by rhein, and imply that MPT may contribute to the anti-cancer activity of rhein. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
