title: Antitumor progression potential of morusin suppressing STAT3 and NFκB in human hepatoma SK-Hep1 cells.
abstract: Morusin is a prenylated flavonoid that has been isolated from the root bark of the mulberry tree (Morus species, Moraceae), a Chinese traditional medicine. It has been synthesized by our laboratory from commercially available phloroglucinol, and has demonstrated to possess antitumor effects of cell lines including A549, MCF-7, and MDA-MB-231. In this study, at non-cytotoxic concentrations, morusin altered invasive morphology and suppressed cell-matrix adhesion, cell motility and cell invasion in SK-Hep1 cells. Morusin also increased the expression of E-cadherin, an epithelial cell junction protein, decreased the expression of vimentin, a mesecnchymal marker, and α2-, α6-, β1- integrin, which regulated cancer attachment and migration. In addition, morusin reduced the activity of matrix metalloproteinase-2 and 9 (MMP-2 and MMP-9), which were involved in extracellular matrix (ECM) degradation and promoting cancer cell invasion. Furthermore, morusin suppressed the signal transducer and activator of transcription 3 (STAT3) and nuclear factor-κB (NFκB) signaling pathways, which modulate the protein expression involved in the invasion process. Finally, morusin decreased the lung colonization of the SK-Hep1 cells in the nude mice. These results indicate morusin possesses antitumor progression potential through suppressing STAT3 and NFκB.
authors.affiliation: Department of Pathlogy, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Wea-Lung
authors.initials: WL
authors.lastname: Lin
authors.affiliation: Department of Chemistry, National Changhua University of Education, 1 Chieng-Derg Road, Changhua 500, Taiwan.
authors.forename: Deng-Yu
authors.initials: DY
authors.lastname: Lai
authors.affiliation: Department of Chemistry, National Changhua University of Education, 1 Chieng-Derg Road, Changhua 500, Taiwan. Electronic address: leeyj@cc.ncue.edu.tw.
authors.forename: Yean-Jang
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: School of Medical Applied Chemistry, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Nai-Fang
authors.initials: NF
authors.lastname: Chen
authors.affiliation: School of Medical Applied Chemistry, Chung Shan Medical University, Taichung, Taiwan; Department of Medical Education, Chung Shan Medical University Hospital, Taichung, Taiwan. Electronic address: tht@csmu.edu.tw.
authors.forename: Tsui-Hwa
authors.initials: TH
authors.lastname: Tseng
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics; D009361:Neoplasm Invasiveness; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D005419:Flavonoids; D016328:NF-kappa B; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C057451:morusin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: Hepatoma; Morusin; NFκB; SK-Hep 1 cells; STAT3; Tumor progression