Phytotherapy research, 2019-05, Vol.33 (5), p.1384-1393
2019
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- Morin enhances auranofin anticancer activity by up‐regulation of DR4 and DR5 and modulation of Bcl‐2 through reactive oxygen species generation in Hep3B human hepatocellular carcinoma cells
- Ist Teil von
- Phytotherapy research, 2019-05, Vol.33 (5), p.1384-1393
- Ort / Verlag
- England: Wiley Subscription Services, Inc
- Erscheinungsjahr
- 2019
- Quelle
- Wiley-Blackwell Journals
- Beschreibungen/Notizen
- Evidence suggests that auranofin (AF) exhibits anticancer activity by inhibiting thioredoxin reductase (TrxR). Here, in this study, we have investigated the synergistic effects of AF and morin and their mechanism for the anticancer effects focusing on apoptosis in Hep3B human hepatocellular carcinoma cells. We assessed the anticancer activities by annexin V/PI double staining, caspase, and TrxR activity assay. Morin enhances the inhibitory effects on TrxR activity of AF as well as reducing cell viability. Annexin V/PI double staining revealed that morin/AF cotreatment induced apoptotic cell death. Morin enhances AF‐induced mitochondrial membrane potential (ΔΨm) loss and cytochrome c release. Further, morin/AF cotreatment upregulated death receptor DR4/DR5, modulated Bcl‐2 family members (upregulation of Bax and downregulation of Bcl‐2), and activated caspase‐3, ‐8, and ‐9. Morin also enhances AF‐induced reactive oxygen species (ROS) generation. The anticancer effects results from caspase‐dependent apoptosis, which was triggered via extrinsic pathway by upregulating TRAIL receptors (DR4/DR5) and enhanced via intrinsic pathway by modulating Bcl‐2 and inhibitor of apoptosis protein family members. These are related to ROS generation. In conclusion, this study provides evidence that morin can enhance the anticancer activity of AF in Hep3B human hepatocellular carcinoma cells, indicating that its combination could be an alternative treatment strategy for the hepatocellular carcinoma.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0951-418XeISSN: 1099-1573DOI: 10.1002/ptr.6329Titel-ID: cdi_proquest_miscellaneous_2194142691
- Format
- –
- Schlagworte
- Animals, Annexin V, Anticancer properties, Antitumor activity, Apoptosis, Apoptosis - drug effects, auranofin, Auranofin - pharmacology, BAX protein, cancer, Carcinoma, Hepatocellular - drug therapy, Carcinoma, Hepatocellular - pathology, Caspase, Caspases - metabolism, Cell death, Cell Line, Tumor, Cell Survival - drug effects, Cell viability, Cytochrome, Cytochrome c, Cytochromes, Cytochromes c - metabolism, Down-Regulation - drug effects, Flavonoids - pharmacology, Hep3B cells, Hepatocellular carcinoma, Humans, Inhibitor of Apoptosis Proteins - metabolism, Liver cancer, Liver Neoplasms - drug therapy, Liver Neoplasms - pathology, Male, Membrane potential, Membrane Potential, Mitochondrial - drug effects, Mitochondria, morin, Proto-Oncogene Proteins c-bcl-2 - metabolism, Rats, Rats, Sprague-Dawley, Reactive oxygen species, Reactive Oxygen Species - metabolism, Receptors, Receptors, TNF-Related Apoptosis-Inducing Ligand - metabolism, Reductase, ROS, Signal Transduction - drug effects, Staining, Synergistic effect, Thioredoxin, Up-regulation, Up-Regulation - drug effects