title: Equol as a potent radiosensitizer in estrogen receptor-positive and -negative human breast cancer cell lines.
abstract: BACKGROUND
  Breast cancer is the most common cause of cancer death among women worldwide, and diet plays an important role in its prevention and progression. Radiotherapy has a limited but important role in the management of nearly every stage of breast cancer. We studied whether equol, the major metabolite of the soybean isoflavone daidzein, could enhance radiosensitivity in two human breast cancer cell lines (T47D and MDA-MB-231).
  
  
  METHODS
  MTT assay was used to examine equol's effect on cell viability. Sensitivity of cells to equol, radiation and a combination of both was determined by colonogenic assays. Induction of apoptosis by equol, radiation and the combination of both was also determined by acridine orange/ethidium bromide double staining fluorescence microscopy. DNA strand breaks were assessed by Comet assay.
  
  
  RESULTS
  MTT assay showed that equol (0.1-350 μM) inhibited MDA-MB-231 and T47D cell growth in a time- and dose-dependent manner. Treatment of cells with equol for 72 h (MDA-MB-231) and 24 h (T47D) was found to inhibit cell growth with IC50 values of 252 μM and 228 μM, respectively. Furthermore, pretreatment of cells with 50 μM equol for 72 h (MDA-MB-231) and 24 h (T47D) sensitized the cells to irradiation. Equol was also found to enhance radiation-induced apoptosis. Comet assay results showed that the radiosensitizing effect of equol was accompanied by increased radiation-induced DNA damages.
  
  
  CONCLUSIONS
  These results suggest for the first time that equol can be considered as a radiosensitizing agent and its effects may be due to increasing cell death following irradiation, increasing the remaining radiation-induced DNA damage and thus reducing the surviving fraction of irradiated cells.
authors.affiliation: Laboratory of Biophysics and Molecular Biology, Institute of Biochemistry and Biophysics, University of Tehran, PO Box 13145-1384, Tehran, Iran.
authors.forename: Bita
authors.initials: B
authors.lastname: Taghizadeh
authors.forename: Laleh
authors.initials: L
authors.lastname: Ghavami
authors.forename: Alireza
authors.initials: A
authors.lastname: Nikoofar
authors.forename: Bahram
authors.initials: B
authors.lastname: Goliaei
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy; D045744:Cell Line, Tumor / Q000187:drug effects / Q000528:radiation effects; D049109:Cell Proliferation / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects / Q000528:radiation effects; D060754:Equol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000378:metabolism*
chemical_list: D011838:Radiation-Sensitizing Agents; D011960:Receptors, Estrogen; D060754:Equol