Back to Search
Start Over
Physcion 8-O-β-glucopyranoside induces mitochondria-dependent apoptosis of human oral squamous cell carcinoma cells via suppressing survivin expression
- Source :
- Acta Pharmacologica Sinica; May 2016, Vol. 37 Issue: 5 p687-697, 11p
- Publication Year :
- 2016
-
Abstract
- Aim:A previous study has shown that physcion 8-O-β-glucopyranoside (PG) derived from Rumex japonicusHoutt causes apoptosis and blocks cell cycle progression in human lung cancer cells. In the present study we investigated the molecular mechanisms underlying PG-induced cancer cell apoptosis.Methods:Human OSCC-derived cell line KB was treated PG (10, 20, 50 μg/mL). Cell apoptosis was detected with flow cytometry. Mitochondrial membrane potential (MMP) and release of cytochome C from mitochondria were measured; the expression of relevant signaling proteins was analyzed using Western blotting or qRT-PCR. For evaluation of in vivo anticancer action, nude mice grafted with KB cells were treated with PG (10, 20, 40 mg·kg−1·d−1, ip) for 24 days.Results:PG dose-dependently suppressed cell proliferation and induced apoptosis in KB cells. PG-induced apoptosis was mediated via the intrinsic mitochondrial pathway, as evidenced by the decreased Bcl-2, increased Bax and Bax/Bcl-2 ratio, as well as the loss of MMP, caspase-9 activation, and increased cytosolic cytochrome c. Furthermore, PG suppressed the expression of survivin, whereas overexpression of survivin markedly attenuated PG-induced apoptosis. Meanwhile PG increased the expression of tumor suppressor PTEN, and decreased p-Akt, p-GSK3β and miR-21 levels. Pharmacological activation of Akt/GSK3β signaling or transfection with miR-21 mimic abolished PG-induced survivin reduction and cell apoptosis. Similar results were observed in PG-treated nude mice grafted with KB cells.Conclusion:Physcion 8-O-β-glucopyranoside induces mitochondria-dependent apoptosis of human OSCC cells by suppressing survivin expression via miR-21/PTEN/Akt/GSK3β signaling pathway.
Details
- Language :
- English
- ISSN :
- 16714083 and 17457254
- Volume :
- 37
- Issue :
- 5
- Database :
- Supplemental Index
- Journal :
- Acta Pharmacologica Sinica
- Publication Type :
- Periodical
- Accession number :
- ejs38749916
- Full Text :
- https://doi.org/10.1038/aps.2015.152