title: Physcion 8-O-β-glucopyranoside suppresses the metastasis of breast cancer in vitro and in vivo by modulating DNMT1.
abstract: BACKGROUND
  The present study is designed to explore the metastasis-inhibitory effect of physcion 8-O-β-glucopyranoside (PG) in human breast cancer, and the mechanisms underlying its role in tumor metastasis.
  
  
  METHODS
  Both in vitro and in vivo studies were conducted. Cell migration and invasion were analyzed by transwell assay. The translocation of β-catenin from the nucleus to cytoplasm membrane was demonstrated by immunofluorescent staining. The expression of signaling molecules was determined by Western blot or qRT-PCR.
  
  
  RESULTS
  The present study showed that PG suppressed the migration, invasion, and EMT of breast cancer cells MDA-MB-231 in a dose-dependent manner. The results also revealed that impairment of the metastatic potential caused by PG was associated with the activation of AMPK and downregulation of both DNMT1 and Sp1. Moreover, the data from the in vivo model also supported the in vitro findings, which showed that inhibition of metastasis by PG was associated with the downregulation of DNMT1 and Sp1 as well as increased level of phosphorylated AMPK.
  
  
  CONCLUSIONS
  The present study showed that PG could suppress the metastasis of breast cancer, which highlighted a novel pharmacological application of this compound. Given the aggressive properties of breast cancer, the current study suggests that PG can serve as a safe therapeutic agent for suppressing breast cancer metastasis, although additional data is necessitated.
authors: Shandong Provincial Hospital Affiliated to Shandong University, Jianan, Shandong 250021, China.
authors: Xia
authors: X
authors: Chen
authors: Shandong Provincial Hospital Affiliated to Shandong University, Jianan, Shandong 250021, China.
authors: Hua
authors: H
authors: Guo
authors: Shandong Provincial Hospital Affiliated to Shandong University, Jianan, Shandong 250021, China. Electronic address: pleonard@126.com.
authors: Fuxia
authors: F
authors: Li
authors: China Pharmaceutical University, Nanjing, Jiangsu 211198, China.
authors: Di
authors: D
authors: Fan
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004642:Emodin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005960:Glucosides / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000556:secondary; D008819:Mice, Nude; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D005960:Glucosides; C000613896:physcion 8-O-glucopyranoside; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human; C000619381:Dnmt1 protein, mouse; D004642:Emodin
keywords: AMPK; Breast cancer; DNMT1; Metastasis; Physcion 8-O-β-glucopyranoside; Sp1