title: Quercetin reverses tamoxifen resistance in breast cancer cells.
abstract: OBJECTIVE
  To investigate the effect of quercetin on the reversal of tamoxifen resistance in breast cancer cells, and explore the underlying mechanism.
  
  
  METHODS
  We established a tamoxifen-resistant breast cancer cell line (MCF-7Ca/TAM-R), and exposed it to different concentrations of quercetin (experimental group 1: 10 μM, group 2: 25 μM, and group 3: 50μM). Each group was further subdivided into 2 subgroups: 1) simultaneous administration of quercetin and 4-hydroxytamoxifen (OHT); 2) sequential administration of quercetin (12-h induction) followed by OHT. No drug exposure and OHT alone were used as controls. We determined cell survival, apoptosis, and expression of ERα (estrogen receptor α) and Her-2 (human epidermal growth factor receptor 2).
  
  
  RESULTS
  With increasing dosage of quercetin, significant decrease in proliferation and increase in apoptosis was observed. Low concentrations of quercetin (10 μM) had no effects. We found no significant difference between simultaneous and sequential mode of drug administration. Further, with increasing dosage of quercetin, we observed a gradual reduction in Her-2 expression and upregulation of ERα. Again, no difference in Her-2 and ERα protein levels between simultaneous and sequential drug administration was noticed.
  
  
  CONCLUSIONS
  Proliferation inhibition and apoptosis in MCF-7Ca/TAM-R cells increase with increasing dosage of quercetin. This suggests that quercetin can reverse tamoxifen resistance in breast cancer cells. The underlying mechanism likely involves upregulation of ERα combined with downregulation of Her-2. However, this effect is independent of whether quercetin and tamoxifen are administered simultaneously or sequentially.
authors.affiliation: Surgical Department of Thyroid and Breast, Affiliated Nanshan Hospital of Guangdong Medical College, Shenzhen, Guangdong, China.
authors.forename: Hongxian
authors.initials: H
authors.lastname: Wang
authors.forename: Linyu
authors.initials: L
authors.lastname: Tao
authors.forename: Ke
authors.initials: K
authors.lastname: Qi
authors.forename: Haoyun
authors.initials: H
authors.lastname: Zhang
authors.forename: Duo
authors.initials: D
authors.lastname: Feng
authors.forename: Wenjun
authors.initials: W
authors.lastname: Wei
authors.forename: Heng
authors.initials: H
authors.lastname: Kong
authors.forename: Tianwen
authors.initials: T
authors.lastname: Chen
authors.forename: Qiusheng
authors.initials: Q
authors.lastname: Lin
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004965:Estrogen Antagonists / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D011794:Quercetin / Q000494:pharmacology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors
chemical_list: D018931:Antineoplastic Agents, Hormonal; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D011794:Quercetin; D018719:Erb-b2 Receptor Tyrosine Kinases; D013629:Tamoxifen; C506487:ESR1 protein, human; C016601:afimoxifene; C508053:ERBB2 protein, human