title: Drug combinations with quercetin: doxorubicin plus quercetin in human breast cancer cells.
abstract: OBJECTIVE
  Doxorubicin is a first-line chemotherapeutic for breast cancer; however, it is associated with severe side effects to non-tumoral tissues. Thus, it is necessary to develop new therapeutic combinations to improve doxorubicin effects at lower concentration of the drug associated with protective effects for non-tumoral cells. In this work, we evaluated whether the plant-derived flavonoid quercetin may represent such an agent.
  
  
  METHODS
  The effects of doxorubicin and quercetin as single agents and in combination were evaluated on cell survival, DNA and protein synthesis, oxidative stress, migratory potential and cytoskeleton and nucleus structure in highly invasive and poorly invasive human breast cancer cells in comparison with non-tumoral human breast cells.
  
  
  RESULTS
  In human breast cancer cells, quercetin potentiated antitumor effects of doxorubicin specifically in the highly invasive breast cancer cells and attenuated unwanted cytotoxicity to non-tumoral cells. Quercetin interfered with cell metabolism, GST activity, cytoskeleton and invasive properties specifically in breast tumor cells compared with non-tumoral breast cells. Doxorubicin induced DNA damage in tumor and non-tumor cells; however, quercetin reduced this damage only in non-tumoral cells, thus offering a protective effect for these cells. Quercetin also induced polynucleation in aggressive tumor cells, which was maintained in combination with doxorubicin.
  
  
  CONCLUSIONS
  By combining quercetin with doxorubicin, an increase in doxorubicin effects was obtained specifically in the highly invasive breast cancer cells, while in non-tumoral cells quercetin reduced doxorubicin cytotoxic side effects. Thus, quercetin associated with doxorubicin demonstrated very promising properties for developing chemotherapeutics combinations for the therapy of breast cancer.
authors.affiliation: Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland.
authors.forename: Davide
authors.initials: D
authors.lastname: Staedler
authors.forename: Elita
authors.initials: E
authors.lastname: Idrizi
authors.forename: Blanka Halamoda
authors.initials: BH
authors.lastname: Kenzaoui
authors.forename: Lucienne
authors.initials: L
authors.lastname: Juillerat-Jeanneret
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D020552:Comet Assay; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology*; D004338:Drug Combinations; D005260:Female; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D011794:Quercetin / Q000008:administration & dosage / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D004338:Drug Combinations; D017382:Reactive Oxygen Species; D004317:Doxorubicin; D011794:Quercetin; D005982:Glutathione Transferase