title: BreastDefend enhances effect of tamoxifen in estrogen receptor-positive human breast cancer in vitro and in vivo.
abstract: BACKGROUND
  Tamoxifen (TAM) has been widely used for the treatment of estrogen receptor (ER)-positive breast cancer and its combination with other therapies is being actively investigated as a way to increase efficacy and decrease side effects. Here, we evaluate the therapeutic potential of co-treatment with TAM and BreastDefend (BD), a dietary supplement formula, in ER-positive human breast cancer.
  
  
  METHODS
  Cell proliferation and apoptosis were determined in ER-positive human breast cancer cells MCF-7 by MTT assay, quantitation of cytoplasmic histone-associated DNA fragments and expression of cleaved PARP, respectively. The molecular mechanism was identified using RNA microarray analysis and western blotting. Tumor tissues from xenograft mouse model were analyzed by immunohistochemistry.
  
  
  RESULTS
  Our data clearly demonstrate that a combination of 4-hydroxytamoxifen (4-OHT) with BD lead to profound inhibition of cell proliferation and induction of apoptosis in MCF-7 cells. This effect is consistent with the regulation of apoptotic and TAM resistant genes at the transcription and translation levels. Importantly, TAM and BD co-treatment significantly enhanced apoptosis, suppressed tumor growth and reduced tumor weight in a xenograft model of human ER-positive breast cancer.
  
  
  CONCLUSIONS
  BD sensitized ER-positive human breast cancer cells to 4-OHT/TAM treatment in vitro and in vivo. BreastDefend can be used in an adjuvant therapy to increase the therapeutic effect of tamoxifen in patients with ER-positive breast cancer.
authors.affiliation: Cancer Research Laboratory, Methodist Research Institute, Indiana University Health, Indianapolis, IN, 46202, USA.|Present address: Department of Food Quality and Safety, School of Engineering, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Shujie
authors.initials: S
authors.lastname: Cheng
authors.affiliation: Cancer Research Laboratory, Methodist Research Institute, Indiana University Health, Indianapolis, IN, 46202, USA.
authors.forename: Victor
authors.initials: V
authors.lastname: Castillo
authors.affiliation: Cancer Research Laboratory, Methodist Research Institute, Indiana University Health, Indianapolis, IN, 46202, USA.
authors.forename: Matt
authors.initials: M
authors.lastname: Welty
authors.affiliation: Cancer Research Laboratory, Methodist Research Institute, Indiana University Health, Indianapolis, IN, 46202, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Alvarado
authors.affiliation: Amitabha Medical Clinic and Healing Center, Santa Rosa, CA, 95401, USA.
authors.forename: Isaac
authors.initials: I
authors.lastname: Eliaz
authors.affiliation: Department of Pathology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
authors.forename: Constance J
authors.initials: CJ
authors.lastname: Temm
authors.affiliation: Department of Pathology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
authors.forename: George E
authors.initials: GE
authors.lastname: Sandusky
authors.affiliation: Cancer Research Laboratory, Methodist Research Institute, Indiana University Health, Indianapolis, IN, 46202, USA. dsliva@dstest-lab.com.|Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, 46202, USA. dsliva@dstest-lab.com.|DSTest Laboratories, Purdue Research Park, 5225 Exploration Drive, Indianapolis, IN, 46241, USA. dsliva@dstest-lab.com.
authors.forename: Daniel
authors.initials: D
authors.lastname: Sliva
mesh_terms: D000277:Adjuvants, Pharmaceutic / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D017209:Apoptosis; D001688:Biological Products / Q000494:pharmacology / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D019587:Dietary Supplements; D019008:Drug Resistance, Neoplasm; D005260:Female; D005658:Fungi; D052138:Genes, Neoplasm; D006801:Humans; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use; D061986:MCF-7 Cells; D019684:Magnoliopsida; D051379:Mice; D011794:Quercetin / Q000494:pharmacology / Q000627:therapeutic use; D011960:Receptors, Estrogen / Q000378:metabolism*; D013629:Tamoxifen / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000277:Adjuvants, Pharmaceutic; D001688:Biological Products; D007211:Indoles; D011960:Receptors, Estrogen; D013629:Tamoxifen; D011794:Quercetin; C016392:3,3'-diindolylmethane
keywords: Apoptosis; BreastDefend; Estrogen receptor; MCF-7; Polybotanical supplement; Tamoxifen; Xenograft model