Generation of reactive oxygen species by a novel berberine–bile acid analog mediates apoptosis in hepatocarcinoma SMMC-7721 cells
| Autor: | Li Zhang, Qingyong Li, Wuna He, Tianyu Liu, Yuangang Zu, Baoyou Zhang |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Carcinoma
Hepatocellular Time Factors Berberine Poly ADP ribose polymerase Active Transport Cell Nucleus Biophysics Antineoplastic Agents Apoptosis DNA Fragmentation Mitochondrion Biochemistry Bile Acids and Salts chemistry.chemical_compound Cytosol Cell Line Tumor Humans Molecular Biology Cell Proliferation Membrane Potential Mitochondrial chemistry.chemical_classification Reactive oxygen species Dose-Response Relationship Drug biology Caspase 3 Cytochrome c Apoptosis Inducing Factor Cytochromes c Depolarization Cell Biology Molecular biology Acetylcysteine Mitochondria Cell biology chemistry Mitochondrial Membranes biology.protein Calcium Poly(ADP-ribose) Polymerases Reactive Oxygen Species |
| Zdroj: | Biochemical and Biophysical Research Communications. 433:432-437 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2013.02.104 |
| Popis: | 2,3-Methenedioxy-9-O-(3'α,7'α-dihydroxy-5'β-cholan-24'-propy-lester)berberine (B4) is a novel berberine-bile acid analog synthesized in our laboratory. Previously, we showed that B4 exerted greater cytotoxicity than berberine in several human cancer cell lines. Therefore, we further evaluated the mechanism governing its anticancer actions in hepatocellular carcinoma SMMC-7721 cells. B4 inhibited the proliferation of SMMC-7721 cells, and stimulated reactive oxygen species (ROS) production and mitochondrial membrane depolarization; anti-oxidant capacity was reduced. B4 also induced the release of cytochrome c from the mitochondria to the cytosol and an increase in poly ADP-ribose polymerase (PARP) cleavage products, reflective of caspase-3 activation. Moreover, B4 induced the nuclear translocation of apoptosis-inducing factor (AIF) and a rise in DNA fragmentation. Pretreatment with the anti-oxidant N-acetylcysteine (NAC) inhibited B4-mediated effects, including cytotoxicity, ROS production, mitochondrial membrane depolarization increase in intracellular Ca2+, cytochrome c release, PARP cleavage, and AIF translocation. Our data suggest that B4 induces ROS-triggered caspase-dependent and caspase-independent apoptosis pathways in SMMC-7721 cells and that ROS production may be a specific potential strategy for treating hepatic carcinoma. |
| Databáze: | OpenAIRE |
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