title: Comparison of inhibitory effects of 17-AAG nanoparticles and free 17-AAG on HSP90 gene expression in breast cancer.
abstract: BACKGROUND
  HSP90 may be overexpressed in cancer cells which are greatly dependent on Hsp90 function. Geldanamycin derivative 17 allylamino-17-demethoxygeldanamycin (17-AAG) inhibits the function and expression of HSP90. 17-AAG has poor water-solubility which is a potential problem for clinical practice. In this study for improving the stability and solubility of molecules in drug delivery systems we used a β-cyclodextrin- 17AAG complex.
  
  
  METHODS
  To assess cytotoxic effects of β-cyclodextrin-17AAG complexes and free 17AAG, colorimetric cell viability (MTT) assays were performed. Cells were treated with equal concentrations of β-cyclodextrin- 17AAG complex and free 17AAG and Hsp90 gene expression levels in the two groups was compared by real-time PCR.
  
  
  RESULTS
  MTT assay confirmed that β-cyclodextrin- 17AAG complex enhanced 17AAG cytotoxicity and drug delivery in T47D breast cancer cells. The level of Hsp90 gene expression in cells treated with β-cyclodextrin- 17AAG complex was lower than that of cells treated with free 17AAG (P=0.001).
  
  
  CONCLUSIONS
  The results demonstrated that β-cyclodextrin- 17AAG complexes are more effective than free 17AAG in down-regulating HSP90 expression due to enhanced β-cyclodextrin-17AAG uptake by cells. Therefore, β-cyclodextrin could be superior carrier for this kind of hydrophobic agent.
authors.affiliation: Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran E-mail : zarghami@tbzmed.ac.ir.
authors.forename: Masoud Gandomkar
authors.initials: MG
authors.lastname: Ghalhar
authors.forename: Abolfazl
authors.initials: A
authors.lastname: Akbarzadeh
authors.forename: Mohammad
authors.initials: M
authors.lastname: Rahmati
authors.forename: Hassan
authors.initials: H
authors.lastname: Mellatyar
authors.forename: Hassan
authors.initials: H
authors.lastname: Dariushnejad
authors.forename: Nosratallah
authors.initials: N
authors.lastname: Zarghami
authors.forename: Amin
authors.initials: A
authors.lastname: Barkhordari
mesh_terms: D016227:Benzoquinones / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000235:genetics*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D006801:Humans; D047029:Lactams, Macrocyclic / Q000008:administration & dosage*; D053758:Nanoparticles; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D047392:beta-Cyclodextrins
chemical_list: D016227:Benzoquinones; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D012333:RNA, Messenger; D047392:beta-Cyclodextrins; C112765:tanespimycin