1. Physcion 8-O-β-glucopyranoside induces mitochondria-dependent apoptosis of human oral squamous cell carcinoma cells via suppressing survivin expression.
- Author
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Liu MD, Xiong SJ, Tan F, and Liu Y
- Subjects
- Animals, Antineoplastic Agents, Phytogenic therapeutic use, Carcinoma, Squamous Cell metabolism, Carcinoma, Squamous Cell pathology, Cell Line, Tumor, Emodin pharmacology, Emodin therapeutic use, Glucosides therapeutic use, Humans, Membrane Potential, Mitochondrial, Mice, Inbred BALB C, Mice, Nude, Mouth Neoplasms metabolism, Mouth Neoplasms pathology, Signal Transduction, Survivin, Antineoplastic Agents, Phytogenic pharmacology, Apoptosis drug effects, Carcinoma, Squamous Cell drug therapy, Emodin analogs & derivatives, Glucosides pharmacology, Inhibitor of Apoptosis Proteins metabolism, Mitochondria physiology, Mouth Neoplasms drug therapy, Repressor Proteins metabolism
- 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.
- Published
- 2016
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