title: Raloxifene and selective cell cycle specific agents: a case for the inclusion of raloxifene in current breast cancer treatment therapies.
abstract: BACKGROUND
  Breast cancer patients are at increased risk of osteoporosis. Contributing factors include age and/or chemotherapy. The selective estrogen modulator, raloxifene (RAL), effective in the prevention of breast cancer and approved for the treatment and prevention of osteoporosis, may prove beneficial in current breast cancer treatment modules. The purpose of this study was to evaluate RAL in combination with 5-fluorouracil (5-FU) and trimetrexate (TMX) to determine the most effective sequence in which to administer these cell cycle specific agents while taking into consideration the cellular mechanism of action. The goal was to maintain cytotoxicity to breast cancer cells and capitalize on the selective estrogen receptor modulatory effects of RAL.
  
  
  METHODS
  MCF-7 cells were exposed to (i) TMX, 5-FU or RAL alone, or (ii) RAL 24 h prior to 5-FU followed 2 h later by TMX, or (iii) 5-FU 2 h prior to TMX followed 24 h later by RAL. The cell viability was determined using the Quick Cell Proliferation Assay.
  
  
  RESULTS
  The growth rate of MCF- 7 cells exposed to early RAL was 68.25 +/- 4.11% that of the control, however, late RAL exposure produced a growth of 34.75 +/- 4.79% that of the control. Late RAL maintained the cytotoxicity of the regimen. The findings were further supported by cell flow cytometry and Western blot analysis data.
  
  
  CONCLUSIONS
  RAL given prior to 5-FU/TMX significantly compromised cytotoxicity to breast cancer cells.
authors.affiliation: Department of Environmental Sciences and Engineering, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Elizabeth B
authors.initials: EB
authors.lastname: Fryar-Tita
authors.forename: Jharna R
authors.initials: JR
authors.lastname: Das
authors.forename: J H
authors.initials: JH
authors.lastname: Davis
authors.forename: J A
authors.initials: JA
authors.lastname: Desoto
authors.forename: Sidney
authors.initials: S
authors.lastname: Green
authors.forename: William M
authors.initials: WM
authors.lastname: Southerland
authors.forename: Donnell
authors.initials: D
authors.lastname: Bowen
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D020849:Raloxifene Hydrochloride / Q000008:administration & dosage*; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage*; D016597:Trimetrexate / Q000008:administration & dosage
chemical_list: D000964:Antimetabolites, Antineoplastic; D050071:Bone Density Conservation Agents; D020845:Selective Estrogen Receptor Modulators; D020849:Raloxifene Hydrochloride; D005472:Fluorouracil; D016597:Trimetrexate