title: Physcion 8-O-β-glucopyranoside induces mitochondria-dependent apoptosis of human oral squamous cell carcinoma cells via suppressing survivin expression.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: School of Dentistry, Shandong University, Ji-nan 250012, China.|School of Stomatology, Qingdao University, Qingdao 266011, China.|Shandong Provincial Key Laboratory of Oral Biomedicine, Shandong University, Ji-nan 250012, China.
authors.forename: Meng-Dong
authors.initials: MD
authors.lastname: Liu
authors.affiliation: School of Dentistry, Shandong University, Ji-nan 250012, China.|Shandong Provincial Key Laboratory of Oral Biomedicine, Shandong University, Ji-nan 250012, China.
authors.forename: Shi-Jiang
authors.initials: SJ
authors.lastname: Xiong
authors.affiliation: School of Stomatology, Qingdao University, Qingdao 266011, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Tan
authors.affiliation: School of Stomatology, Qingdao University, Qingdao 266011, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D004642:Emodin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005960:Glucosides / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008928:Mitochondria / Q000502:physiology*; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction; D000077022:Survivin
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C107489:BIRC5 protein, human; C117749:Birc5 protein, mouse; D005960:Glucosides; D051034:Inhibitor of Apoptosis Proteins; D012097:Repressor Proteins; D000077022:Survivin; C000613896:physcion 8-O-glucopyranoside; D004642:Emodin