title: The inhibitory mechanism by curcumin on the Zac1-enhanced cyclin D1 expression in human keratinocytes.
abstract: BACKGROUND
  ZAC, a zinc finger protein regulating cell cycle arrest and apoptosis, mRNA was found highly expressed in the hyper-proliferative epidermal compartment of psoriatic skin. On the other hand, curcumin has been tried for treatment of psoriasis partly due to its anti-proliferative property.
  
  
  OBJECTIVE
  Since cyclin D1 is a positive regulator for cell-cycle progression and its expression can be inhibited by curcumin, we would like to test whether the expression of cyclin D1 can be affected by Zac1. The cross-talk between curcumin and Zac1 upon the regulation of cyclin D1 expression will also be explored in the HaCaT cell line.
  
  
  METHODS
  Cyclin D1 promoter luciferase reporter was used to measure the transcriptional activity of Zac1 in the absence or presence of curcumin treatment for HaCaT cells. Likewise, RT-PCR, western blotting and flow cytometry were employed to evaluate the expression of Zac1, cyclin D1 and other negative regulators of S phase entry in cell-cycle.
  
  
  RESULTS
  Zac1 enhances the expression of cyclin D1, but curcumin decreases both the expression of Zac1 and cyclin D1. Interestingly, Zac1-induced cyclin D1 promoter activity is abolished by curcumin. Supportively, curcumin indeed exhibits an inhibitory effect to prevent cultured keratinocytes from entry into S phase in the cell cycle.
  
  
  CONCLUSIONS
  These findings revealed that Zac1 modulates not only cell differentiation and apoptosis but also cell proliferation. The experimental results implied that curcumin may inhibit the expression of ZAC, consequently down-regulate the cyclin D1 expression and decelerate cell-cycle progression of psoriatic keratinocytes.
authors.affiliation: Department of Dermatology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Chih-Tsung
authors.initials: CT
authors.lastname: Hung
authors.affiliation: Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Shih-Ming
authors.initials: SM
authors.lastname: Huang
authors.affiliation: Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Hsiao-Chun
authors.initials: HC
authors.lastname: Cheng
authors.affiliation: Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Shu-Ting
authors.initials: ST
authors.lastname: Liu
authors.affiliation: Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Yung-Lung
authors.initials: YL
authors.lastname: Chang
authors.affiliation: School of Nursing, National Defense Medical Center, Taipei, Taiwan; School of Nursing, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Ying-Chun
authors.initials: YC
authors.lastname: Liu
authors.affiliation: Department of Dermatology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan. Electronic address: ades0431@ms38.hinet.net.
authors.forename: Wei-Ming
authors.initials: WM
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D018797:Cell Cycle Proteins / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D003474:Curcumin / Q000494:pharmacology*; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D006801:Humans; D015603:Keratinocytes; D011401:Promoter Regions, Genetic / Q000187:drug effects; D059807:S Phase Cell Cycle Checkpoints / Q000187:drug effects*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D025521:Tumor Suppressor Proteins / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; C106464:PLAGL1 protein, human; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D019938:Cyclin D1; D003474:Curcumin
keywords: Curcumin; Cyclin D1; Keratinocyte; Psoriasis; Zac1