title: Zyflamend, a polyherbal mixture, down regulates class I and class II histone deacetylases and increases p21 levels in castrate-resistant prostate cancer cells.
abstract: BACKGROUND
  Zyflamend, a mixture containing extracts of ten herbs, has shown promise in a variety of preclinical cancer models, including prostate cancer. The current experiments were designed to investigate the effects of Zyflamend on the expression of class I and II histone deacetylases, a family of enzymes known to be over expressed in a variety of cancers.
  
  
  METHODS
  CWR22Rv1 cells, a castrate-resistant prostate cancer cell line, were treated with Zyflamend and the expression of class I and II histone deacetylases, along with their downstream target the tumor suppressor gene p21, was investigated. Involvement of p21 was confirmed with siRNA knockdown and over expression experiments.
  
  
  RESULTS
  Zyflamend down-regulated the expression of all class I and II histone deacetylases where Chinese goldthread and baikal skullcap (two of its components) appear to be primarily responsible for these results. In addition, Zyflamend up regulated the histone acetyl transferase complex CBP/p300, potentially contributing to the increase in histone 3 acetylation. Expression of the tumor suppressor gene p21, a known downstream target of histone deacetylases and CBP/p300, was increased by Zyflamend treatment and the effect on p21 was, in part, mediated through Erk1/2. Knockdown of p21 with siRNA technology attenuated Zyflamend-induced growth inhibition. Over expression of p21 inhibited cell growth and concomitant treatment with Zyflamend enhanced this effect.
  
  
  CONCLUSIONS
  Our results suggest that the extracts of this polyherbal combination increase histone 3 acetylation, inhibit the expression of class I and class II histone deacetylases, increase the activation of CBP/p300 and inhibit cell proliferation, in part, by up regulating p21 expression.
authors.forename: E-Chu
authors.initials: EC
authors.lastname: Huang
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhao
authors.forename: Guoxun
authors.initials: G
authors.lastname: Chen
authors.forename: Seung Joon
authors.initials: SJ
authors.lastname: Baek
authors.forename: Michael F
authors.initials: MF
authors.lastname: McEntee
authors.forename: Steven
authors.initials: S
authors.lastname: Minkin
authors.forename: John P
authors.initials: JP
authors.lastname: Biggerstaff
authors.affiliation: Department of Nutrition, University of Tennessee, 1215 West Cumberland Avenue, Room 229 Jessie Harris Building, Knoxville, TN 37996, USA. jwhelan@utk.edu.
authors.forename: Jay
authors.initials: J
authors.lastname: Whelan
mesh_terms: D000107:Acetylation; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D039323:Coptis; D015536:Down-Regulation; D006655:Histone Deacetylases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D008297:Male; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D031363:Scutellaria; D015533:Transcriptional Activation; D025521:Tumor Suppressor Proteins / Q000187:drug effects / Q000378:metabolism*; D015854:Up-Regulation; D050880:p300-CBP Transcription Factors / Q000378:metabolism
chemical_list: D006657:Histones; D010936:Plant Extracts; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins; C519312:Zyflamend; D050880:p300-CBP Transcription Factors; D006655:Histone Deacetylases