B4G2 induces mitochondrial apoptosis by the ROS-mediated opening of Ca(2+)-dependent permeability transition pores
| Autor: | Ming-Kuen Tang, Nan Yao, Wei-Min Chen, Ping Lan, Yong Li, Zhe Yao, Dao-Lu Liu, Ying-Jie Li, Zhang Dongmei, Ye Wencai, Zhe-Sheng Chen, Anita Yiu |
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| Rok vydání: | 2015 |
| Předmět: |
Carcinoma
Hepatocellular Physiology Population Apoptosis Mitochondrial apoptosis-induced channel Mitochondrial Membrane Transport Proteins Calcium in biology lcsh:Physiology lcsh:Biochemistry Mitochondrial membrane transport protein Cell Line Tumor Humans lcsh:QD415-436 education HepG2 cells Cell Proliferation chemistry.chemical_classification Membrane Potential Mitochondrial Reactive oxygen species education.field_of_study biology lcsh:QP1-981 Mitochondrial Permeability Transition Pore Cytochrome c Liver Neoplasms Mitochondrial pathway ROS Hep G2 Cells Molecular biology digestive system diseases Triterpenes Cell biology Gene Expression Regulation Neoplastic chemistry Mitochondrial permeability transition pore 23-hydroxybetulinic acid derivative PT pore biology.protein Calcium Reactive Oxygen Species |
| Zdroj: | Cellular Physiology and Biochemistry, Vol 37, Iss 3, Pp 838-852 (2015) |
| ISSN: | 1421-9778 |
| Popis: | Background/Aims: Hepatocellular carcinoma (HCC) is the most common type of liver cancer. At present, only sorafenib is approved to treat HCC. In this study, we found that a 23-hydroxybetulinic acid derivative, B4G2, exhibited potent antiproliferative activity in HCC cell lines. Methods: We used four HCC cell lines (HepG2, HepG2/ADM, Hep3B and Bel-7402) to evaluate the anti-tumour activity and explore underlying mechanisms by which B4G2 induces apoptosis. Results: Among these cell lines, HepG2 showed the highest sensitivity to B4G2. HepG2 cells treated with B4G2 showed a depolarized mitochondrial membrane potential, released cytochrome c, activated caspase-9 and caspase-3 and cleaved poly ADP-ribose polymerase (PARP). However, Z-VAD-FMK, a pan-caspase inhibitor, did not attenuate B4G2-induced apoptosis, implying that the induction of mitochondrial apoptosis by B4G2 may be independent of caspases. Moreover, pre-treatment with MgCl2, a blocker of Ca2+-dependent permeability transition (PT) pores, attenuated the depolarization of the mitochondrial potential and decreased the population of apoptotic cells, indicating that B4G2-induced apoptosis was partly dependent on the opening of the Ca2+-dependent PT pores. B4G2 also increased the levels of intracellular calcium and reactive oxygen species (ROS). Furthermore, an ROS scavenger, N-acetyl-cysteine (NAC), markedly decreased the accumulation of intracellular calcium and apoptosis. Conclusion: This is the first demonstration that B4G2 inhibits the growth of HCC cells and induces mitochondrial apoptosis in hepatocellular carcinoma cells by the ROS-mediated opening of Ca2+-dependent permeability transition pores. |
| Databáze: | OpenAIRE |
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