title: Epithelial-mesenchymal transition, a novel target of sulforaphane via COX-2/MMP2, 9/Snail, ZEB1 and miR-200c/ZEB1 pathways in human bladder cancer cells.
abstract: Metastasis and recurrence of bladder cancer are the main reasons for its poor prognosis and high mortality rates. Because of its biological activity and high metabolic accumulation in urine, sulforaphane, a phytochemical exclusively occurring in cruciferous vegetables, has a powerful and specific potential for preventing bladder cancer. In this paper, sulforaphane is shown to significantly suppress a variety of biochemical pathways including the attachment, invasion, migration and chemotaxis motion in malignant transitional bladder cancer T24 cells. Transfection with cyclooxygenase-2 (COX-2) overexpression plasmid largely abolished inhibition of MMP2/9 expression as well as cell invasive capability by sulforaphane. Moreover, sulforaphane inhibited the epithelial-to-mesenchymal transition (EMT) process which underlies tumor cell invasion and migration mediated by E-cadherin induction through reducing transcriptional repressors, such as ZEB1 and Snail. Under conditions of over-expression of COX-2 and/or MMP2/9, sulforaphane was still able to induce E-cadherin or reduce Snail/ZEB1 expression, suggesting that additional pathways might be involved. Further studies indicated that miR-200c played a role in the regulation of E-cadherin via the ZEB1 repressor but not by the Snail repressor. In conclusion, the EMT and two recognized signaling pathways (COX-2/MMP2,9/ ZEB1, Snail and miR-200c/ZEB1) are all targets for sulforaphane. This study indicated that sulforaphane may possess therapeutic potential in preventing recurrence of human bladder cancer.
authors.affiliation: School of Food Science and Engineering, Harbin Institute of Technology, Harbin, Heilongjiang 150090, China.
authors.forename: Yujuan
authors.initials: Y
authors.lastname: Shan
authors.forename: Lanwei
authors.initials: L
authors.lastname: Zhang
authors.forename: Yongping
authors.initials: Y
authors.lastname: Bao
authors.forename: Baolong
authors.initials: B
authors.lastname: Li
authors.forename: Canxia
authors.initials: C
authors.lastname: He
authors.forename: Mingming
authors.initials: M
authors.lastname: Gao
authors.forename: Xue
authors.initials: X
authors.lastname: Feng
authors.forename: Weili
authors.initials: W
authors.lastname: Xu
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Zhang
authors.forename: Shuran
authors.initials: S
authors.lastname: Wang
mesh_terms: D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism*; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors; D013454:Sulfoxides; D014157:Transcription Factors / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000473:pathology*; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D018398:Homeodomain Proteins; D017879:Isothiocyanates; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D000071250:Snail Family Transcription Factors; D013454:Sulfoxides; D014157:Transcription Factors; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1; D051546:Cyclooxygenase 2; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C016766:sulforaphane