Drug design, development and therapy, 2015-01, Vol.9 (default), p.5611-5622
2015
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- Autor(en) / Beteiligte
- Titel
- Paeoniflorin inhibits human glioma cells via STAT3 degradation by the ubiquitin-proteasome pathway
- Ist Teil von
- Drug design, development and therapy, 2015-01, Vol.9 (default), p.5611-5622
- Ort / Verlag
- New Zealand: Dove Medical Press Limited
- Erscheinungsjahr
- 2015
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- We investigated the underlying mechanism for the potent proapoptotic effect of paeoniflorin (PF) on human glioma cells in vitro, focusing on signal transducer and activator of transcription 3 (STAT3) signaling. Significant time- and dose-dependent apoptosis and inhibition of proliferation were observed in PF-treated U87 and U251 glioma cells. Expression of STAT3, its active form phosphorylated STAT3 (p-STAT3), and several downstream molecules, including HIAP, Bcl-2, cyclin D1, and Survivin, were significantly downregulated upon PF treatment. Overexpression of STAT3 induced resistance to PF, suggesting that STAT3 was a critical target of PF. Interestingly, rapid downregulation of STAT3 was consistent with its accelerated degradation, but not with its dephosphorylation or transcriptional modulation. Using specific inhibitors, we demonstrated that the prodegradation effect of PF on STAT3 was mainly through the ubiquitin-proteasome pathway rather than via lysosomal degradation. These findings indicated that PF-induced growth suppression and apoptosis in human glioma cells through the proteasome-dependent degradation of STAT3.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1177-8881eISSN: 1177-8881DOI: 10.2147/DDDT.S93912Titel-ID: cdi_doaj_primary_oai_doaj_org_article_55c2f6e2dd114b4baffaffd2f630bbfe
- Format
- –
- Schlagworte
- Antineoplastic Agents, Phytogenic - pharmacology, Apoptosis, Apoptosis - drug effects, Bcl-2 protein, Brain Neoplasms - drug therapy, Brain Neoplasms - enzymology, Brain Neoplasms - genetics, Brain Neoplasms - pathology, Cancer therapies, Cell cycle, Cell Line, Tumor, Cell proliferation, Cell Proliferation - drug effects, Chinese medicine, Cyclin D1, Degradation, Dephosphorylation, Dose-Response Relationship, Drug, Glioma, Glioma - drug therapy, Glioma - enzymology, Glioma - genetics, Glioma - pathology, Glioma cells, Gliomas, Glucosides - pharmacology, Health aspects, Hospitals, Humans, Immunoglobulins, Lysosomes, Medical prognosis, Monoterpenes - pharmacology, Original Research, Phosphatase, Phosphorylation, Plant products, Proteasome Endopeptidase Complex - metabolism, Proteasomes, Proteins, Proteolysis, Signal Transduction - drug effects, Stat3 protein, STAT3 Transcription Factor - genetics, STAT3 Transcription Factor - metabolism, Survivin, Time dependence, Time Factors, Transcription, Transcription factors, Transfection, Ubiquitin, Ubiquitin - metabolism, Ubiquitin-proteasome system, Ubiquitination