title: Sulforaphane inhibits invasion by phosphorylating ERK1/2 to regulate E-cadherin and CD44v6 in human prostate cancer DU145 cells.
abstract: Advanced prostate cancer has highly invasive potential, which may lead to metastasis associated with poor prognosis. Sulforaphane (SFN), abundant in cruciferous vegetables, exhibited effective resistance to carcinogenesis in a variety of tumors. The aim of the present study was to investigate whether SFN inhibited invasion in human prostate cancer cells via sustained activation of ERK1/2 and downstream signaling by an invasion assay, gelatin zymography and western blot analysis. The results showed that SFN inhibited invasion and we characterized the underlying mechanisms in human DU145 prostate cancer cells. SFN (15 µM) changed cell morphology leading to short‑cell pseudopodia which may suppress tumor migration and invasion. The Transwell assay showed that SFN phosphorylated ERK1/2 in a dose- and time-dependent manner and significantly inhibited cell invasion, while the effect was reduced by the ERK1/2 blocker PD98059 (25 µM). Furthermore, these effects contributed to the upregulation of E-cadherin and the downregulation of CD44v6 and were eradicated by PD98059. Western blot analysis and gelatin zymography showed that SFN decreased the expression and activity of MMP-2. Thus, SFN inhibited invasion by activating ERK1/2 to upregulate E-cadherin and downregulate CD44v6, thereby reducing MMP-2 expression and activity. E-cadherin is an invasion inhibitor, while CD44v6 and MMP-2 are invasion promoters. Therefore, SFN is a prospective therapeutic agent that may be used to prevent invasion in prostate cancer.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, P.R. China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Peng
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, P.R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Tian
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, P.R. China.
authors.forename: Gaoxiang
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing, P.R. China.
authors.forename: Chunliu
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Geng
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, P.R. China.
authors.forename: Sai
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
mesh_terms: D015820:Cadherins / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis* / Q000235:genetics; D017879:Isothiocyanates / Q000008:administration & dosage*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis* / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000235:genetics; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D013454:Sulfoxides
chemical_list: C112697:CD44v6 antigen; D015820:Cadherins; D018960:Hyaluronan Receptors; D017879:Isothiocyanates; D013454:Sulfoxides; D020778:Matrix Metalloproteinase 2; C016766:sulforaphane