title: The addition of a pregnenolone pendant group enhances the anticancer properties of titanocene dichloride in a mcf-7 xenograft model.
abstract: OBJECTIVE
  Titanocene dichloride held great promise as a chemotherapeutic compound in pre-clinical studies. However, subsequent clinical trials revealed hepatoxicity and nephrotoxicity, which limited its use in clinical applications. Therefore, we used steroid pendant groups to improve the targeting of titanocene in MCF-7 breast cancer cells, and demonstrated a 10-fold lower effective dose compared to titanocene in in vitro assays. The aim of the present study was to test the efficacy of a titanocene functionalized with pregnenolone (Ti-Preg) in an in vivo breast cancer model.
  
  
  METHODS
  Xenografts from the MCF7 breast cancer cell line were implanted into athymic nu/nu mice to evaluate the potential of Ti-Preg as an anti-breast cancer agent.
  
  
  RESULTS
  Ti-Preg demonstrated significant inhibition of MCF-7 tumor growth when compared to vehicle and to titanocene controls.
  
  
  CONCLUSIONS
  Our findings demonstrate the potential of steroid pendent groups for targeting chemotherapeutics to steroid hormone-dependent cancer.
authors.affiliation: Department of Biology, University of Puerto Rico - Reciento Rio Piedras, PO Box 23360, San Juan, Puerto Rico 00931. valancew@gmail.com.
authors.forename: Gladiany
authors.initials: G
authors.lastname: Ramos
authors.forename: Yaliz
authors.initials: Y
authors.lastname: Loperena
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ortiz
authors.forename: Fiorella
authors.initials: F
authors.lastname: Reyes
authors.forename: Ada
authors.initials: A
authors.lastname: Szeto
authors.forename: Jose
authors.initials: J
authors.lastname: Vera
authors.forename: Javier
authors.initials: J
authors.lastname: Velez
authors.forename: Jessica
authors.initials: J
authors.lastname: Morales
authors.forename: Deborah
authors.initials: D
authors.lastname: Morrero
authors.forename: Linnette
authors.initials: L
authors.lastname: Castillo
authors.forename: Surangani
authors.initials: S
authors.lastname: Dharmawardhane
authors.forename: Enrique
authors.initials: E
authors.lastname: Melendez
authors.forename: A Valance
authors.initials: AV
authors.lastname: Washington
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D061986:MCF-7 Cells; D051379:Mice; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D011284:Pregnenolone / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D011284:Pregnenolone; C020528:titanocene dichloride
keywords: TLT-1; Titanocene; breast cancer; steroid pendant groups; titanocenyl-pregnenolone