Matrine induces caspase-independent program cell death in hepatocellular carcinoma through bid-mediated nuclear translocation of apoptosis inducing factor
| Autor: | Zhigang Deng, Ya Gao, Gang Song, Bing Zhang, Yan-yan Zhan, Hanwei Cao, Wenqing Zhang, Minying Xu, Qiao Wang, Tianhui Hu, Huan Zhou |
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| Rok vydání: | 2014 |
| Předmět: |
Cancer Research
Programmed cell death Carcinoma Hepatocellular Hepatocellular carcinoma Necroptosis Blotting Western Active Transport Cell Nucleus Mice Nude Antineoplastic Agents Apoptosis Mitochondrion Biology Transfection Caspase-independent PCD Bid AIF Mice chemistry.chemical_compound Alkaloids Matrine medicine Animals Humans Matrines Cell Nucleus Mice Inbred BALB C Research Liver Neoplasms Apoptosis Inducing Factor Hep G2 Cells Flow Cytometry medicine.disease Immunohistochemistry Xenograft Model Antitumor Assays digestive system diseases Oncology chemistry Immunology Cancer cell Cancer research Molecular Medicine Apoptosis-inducing factor Female Tumor necrosis factor alpha biological phenomena cell phenomena and immunity Quinolizines BH3 Interacting Domain Death Agonist Protein |
| Zdroj: | Molecular Cancer |
| ISSN: | 1476-4598 |
| Popis: | Matrine, a clinical drug in China, has been used to treat viral hepatitis, cardiac arrhythmia and skin inflammations. Matrine also exhibits chemotherapeutic potential through its ability to trigger cancer cell death. However, the mechanisms involved are still largely unknown. The objective of this study was to investigate the major determinant for the cell death induced by matrine in human hepatocellular carcinoma. We use human hepatocellular carcinoma cell line HepG2 and human hepatocellular carcinoma xenograft in nude mice as models to study the action of matrine in hepatocellular cancers. We found that caspase-dependent and -independent Program Cell Death (PCD) occurred in matrine-treated HepG2 cells, accompanied by the decreasing of mitochondrial transmembrane potential and the increasing ROS production. Further studies showed that AIF released from the mitochondria to the nucleus, and silencing of AIF reduced the caspase-independent PCD induced by matrine. What's more, AIF nuclear translocation, and the subsequent cell death as well, was prevented by Bid inhibitor BI-6C9, Bid-targeted siRNA and ROS scavenger Tiron. In the in vivo study, matrine significantly attenuated tumor growth with AIF release from mitochondria into nucleus in nude mice. These data imply that matrine potently induce caspase-independent PCD in HepG2 cells through Bid-mediated AIF translocation. |
| Databáze: | OpenAIRE |
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